Kern Medical Center

The metabolic syndrome is a common precursor of cardiovascular disease and type 2 diabetes that is characterized by the clustering of insulin resistance, dyslipidemia, and increased blood pressure. In humans, mutations in the peroxisome proliferator-activated receptor-gamma (PPARgamma) have been reported to cause the full-blown metabolic syndrome, and drugs that activate PPARgamma have proven to be effective agents for the prevention and treatment of insulin resistance and type 2 diabetes. Here we report that telmisartan, a structurally unique angiotensin II receptor antagonist used for the treatment of hypertension, can function as a partial agonist of PPARgamma; influence the expression of PPARgamma target genes involved in carbohydrate and lipid metabolism; and reduce glucose, insulin, and triglyceride levels in rats fed a high-fat, high-carbohydrate diet. None of the other commercially available angiotensin II receptor antagonists appeared to activate PPARgamma when tested at concentrations typically achieved in plasma with conventional oral dosing. In contrast to ordinary antihypertensive and antidiabetic agents, molecules that can simultaneously block the angiotensin II receptor and activate PPARgamma have the potential to treat both hemodynamic and biochemical features of the metabolic syndrome and could provide unique opportunities for the prevention and treatment of diabetes and cardiovascular disease in high-risk populations.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure.

Pancreatic and peripancreatic necrosis may result in significant morbidity and mortality in patients with acute pancreatitis. Many recommendations have been made for management of necrotizing pancreatitis, but no published guidelines have incorporated the many recent developments in minimally invasive techniques for necrosectomy. Hence, a multidisciplinary conference was convened to develop a consensus on interventions for necrotizing pancreatitis. Participants included most international experts from multiple disciplines. The evidence for efficacy of interventions was reviewed, presentations were given by experts, and a consensus was reached on each topic. In summary, intervention is primarily indicated for infected necrosis, less often for symptomatic sterile necrosis, and should ideally be delayed as long as possible, preferably 4 weeks or longer after the onset of disease, for better demarcation and liquefaction of the necrosis. Both the step-up approach using percutaneous drainage followed by minimally invasive video-assisted retroperitoneal debridement and per-oral endoscopic necrosectomy have been shown to have superior outcomes to traditional open necrosectomy with respect to short-term and long-term morbidity and are emerging as treatments of choice. Applicability of these techniques depends on the availability of specialized expertise and a multidisciplinary team dedicated to the management of severe acute pancreatitis and its complications.

The objective of this article is to present to physicians an update on plant-based diets. Concerns about the rising cost of health care are being voiced nationwide, even as unhealthy lifestyles are contributing to the spread of obesity, diabetes, and cardiovascular disease. For these reasons, physicians looking for cost-effective interventions to improve health outcomes are becoming more involved in helping their patients adopt healthier lifestyles. Healthy eating may be best achieved with a plant-based diet, which we define as a regimen that encourages whole, plant-based foods and discourages meats, dairy products, and eggs as well as all refined and processed foods. We present a case study as an example of the potential health benefits of such a diet. Research shows that plant-based diets are cost-effective, low-risk interventions that may lower body mass index, blood pressure, HbA1C, and cholesterol levels. They may also reduce the number of medications needed to treat chronic diseases and lower ischemic heart disease mortality rates. Physicians should consider recommending a plant-based diet to all their patients, especially those with high blood pressure, diabetes, cardiovascular disease, or obesity.

BACKGROUND: In previous open-label noncomparative clinical trials, both fluconazole and itraconazole were effective therapy for progressive forms of coccidioidomycosis. OBJECTIVE: To determine whether fluconazole or itraconazole is superior for treatment of nonmeningeal progressive coccidioidal infections. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 7 treatment centers in California, Arizona, and Texas. PATIENTS: 198 patients with chronic pulmonary, soft tissue, or skeletal coccidioidal infections. INTERVENTION: Oral fluconazole, 400 mg/d, or itraconazole, 200 mg twice daily. MEASUREMENTS: After 4, 8, and 12 months, a predefined scoring system was used to assess severity of infection. Findings were compared with those at baseline. RESULTS: Overall, 50% of patients (47 of 94) and 63% of patients (61 of 97) responded to 8 months of treatment with fluconazole and itraconazole, respectively (difference, 13 percentage points [95% CI, -2 to 28 percentage points]; P = 0.08). Patients with skeletal infections responded twice as frequently to itraconazole as to fluconazole. By 12 months, 57% of patients had responded to fluconazole and 72% had responded to itraconazole (difference, 15 percentage points [CI, 0.003 to 30 percentage points]; P = 0.05). Soft tissue disease was associated with increased likelihood of response, as in previous studies. Azole drug was detected in serum specimens from all but 3 patients; however, drug concentrations were not helpful in predicting outcome. Relapse rates after discontinuation of therapy did not differ significantly between groups (28% after fluconazole treatment and 18% after itraconazole treatment). Both drugs were well tolerated. CONCLUSIONS: Neither fluconazole nor itraconazole showed statistically superior efficacy in nonmeningeal coccidioidomycosis, although there is a trend toward slightly greater efficacy with itraconazole at the doses studied.

The development of clinical symptoms in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE) involves T-cell activation and migration into the central nervous system, production of glial-derived inflammatory molecules, and demyelination and axonal damage. Ligands of the peroxisome proliferator-activated receptor (PPAR) exert anti-inflammatory effects on glial cells, reduce proliferation and activation of T cells, and induce myelin gene expression. We demonstrate in two models of EAE that orally administered PPARgamma ligand pioglitazone reduced the incidence and severity of monophasic, chronic disease in C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein peptide and of relapsing disease in B10.Pl mice immunized with myelin basic protein. Pioglitazone also reduced clinical signs when it was provided after disease onset. Clinical symptoms were reduced by two other PPARgamma agonists, suggesting a role for PPARgamma activation in protective effects. The suppression of clinical signs was paralleled by decreased lymphocyte infiltration, lessened demyelination, reduced chemokine and cytokine expression, and increased inhibitor of kappa B (IkB) expression in the brain. Pioglitazone also reduced the antigen-dependent interferon-gamma production from EAE-derived T cells. These results suggest that orally administered PPARgamma agonists could provide therapeutic benefit in demyelinating disease.

Management of patients diagnosed with coccidioidomycosis involves defining the extent of infection and assessing host factors that predispose to disease severity. Patients with relatively localized acute pulmonary infections and no risk factors for complications often require only periodic reassessment to demonstrate resolution of their self-limited process. On the other hand, patients with extensive spread of infection or at high risk of complications because of immunosuppression or other preexisting factors require a variety of treatment strategies that may include antifungal therapy, surgical debridement, or both. Amphotericin B is often selected for treatment of patients with respiratory failure due to Coccidioides immitis or rapidly progressive coccidioidal infections. With other more chronic manifestations of coccidioidomycosis, treatment with fluconazole, itraconazole, or ketoconazole is common. Duration of therapy often ranges from many months to years, and, for some patients, chronic suppressive therapy is needed to prevent relapses.

By ignoring the root causes of disease and neglecting to prioritize lifestyle measures for prevention, the medical community is placing people at harm. Advanced nations, influenced by a Western lifestyle, are in the midst of a health crisis, resulting largely from poor lifestyle choices. Epidemiologic, ecologic, and interventional studies have repeatedly indicated that most chronic illnesses, including cardiovascular disease, cancer, and type 2 diabetes, are the result of lifestyles fueled by poor nutrition and physical inactivity.In this article, we describe the practice of lifestyle medicine and its powerful effect on these modern instigators of premature disability and death. We address the economic benefits of prevention-based lifestyle medicine and its effect on our health care system: A system on the verge of bankruptcy. We recommend vital changes to a disastrous course. Many deaths and many causes of pain, suffering, and disability could be circumvented if the medical community could effectively implement and share the power of healthy lifestyle choices. We believe that lifestyle medicine should become the primary approach to the management of chronic conditions and, more importantly, their prevention. For future generations, for our own health, and for the Hippocratic Oath we swore to uphold ("First do no harm"), the medical community must take action. It is our hope that the information presented will inspire our colleagues to pursue lifestyle medicine research and incorporate such practices into their daily care of patients. The time to make this change is now.

Fluconazole has been associated with various teratisms in animals, including craniofacial ossification defects, thin, wavy ribs, and renal pelvis defects. We describe three infants born to women who were receiving fluconazole through or beyond the first trimester of pregnancy. All of the infants had congenital anomalies; no other drug was implicated. Only one of the three infants survived. Their anomalies, similar to those observed in animal studies, were largely craniofacial, skeletal (i.e., thin, wavy ribs and ossification defects), and cardiac. One of these infants was previously reported as having Antley-Bixler syndrome; however, given the chronology described herein and the similarity of this infant to the others, we conclude that her deformities also represent the potent teratogenic effect of fluconazole.

The complexity of head and neck cancers (HNC) mandates a multidisciplinary approach and radiation therapy (RT) plays a critical role in the optimal management of patients with HNC, either as frontline or adjuvant treatment postoperatively. The advent of both definitive and post-operative RT has significantly improved the outcomes of patients with HNC. Herein, we discuss the role of postoperative RT in different subtypes of HNC, its side effects, and the importance of surveillance. The treatment regions discussed in this paper are the oral cavity, nasopharynx, paranasal sinus cavity, oropharynx, larynx and hypopharynx. Multiple studies that demonstrate the importance of definitive and/or postoperative RT, which led to an improved outlook of survival for HNC patients will be discussed.

Surveillance for coccidioidomycosis (CM) and a case-control study for risk factors among adults were conducted in Kern County, California. From January 1995 through December 1996, 905 cases of CM were identified, for an annual incidence of 86 cases per 100,000 population. A total of 380 adults were enrolled in the case-control study: 77 had severe pulmonary disease, 33 had disseminated disease, and 270 control patients had mild disease. Independent risk factors for severe pulmonary disease included diabetes, recent history of cigarette smoking, income of < $15,000 per year, and older age. Oral antifungal therapy before hospitalization was associated with a reduced risk of CM pneumonia. Risk factors for disseminated disease were black race, income of < $15,000 per year, and pregnancy. Early treatment of CM with oral antifungal agents may prevent severe pulmonary disease in groups considered to be at high risk, such as elderly individuals, persons with diabetes, and smokers. Persons at risk for severe CM may benefit from vaccination once an effective CM vaccine is available.

BACKGROUND: Psoriasis is often treated with agents that activate nuclear hormone receptors for glucocorticoids, retinoids, and vitamin D. The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a related nuclear hormone receptor that can be activated by its ligands, including the thiazolidinediones. OBJECTIVE: To assess whether treatment with troglitazone, a currently available thiazolidinedione used to treat diabetes mellitus, has an effect on psoriasis in normoglycemic patients and whether ligands for PPARgamma have an effect on models of psoriasis. DESIGN: Open-label administration of troglitazone in patients with psoriasis and evaluation of drug actions in cellular, organ, and transplant models of psoriasis. SETTING: University and community hospital outpatient departments and university laboratories. PATIENTS: Patients with chronic, stable plaque psoriasis and control subjects. Five patients with psoriasis received troglitazone (none withdrew); 10 different untreated patients and 10 controls provided tissue samples. INTERVENTIONS: Oral troglitazone therapy at various dosages in patients with psoriasis; also, use of troglitazone, ciglitazone, and 15-deoxy-delta-12,14-prostaglandinJ2 in psoriasis models. MAIN OUTCOME MEASURES: Investigator-determined clinical results in patients and cell counts and histological evidence in models. RESULTS: All patients' psoriasis improved substantially during troglitazone therapy. Peroxisome proliferator-activated receptor-gamma was expressed in human keratinocytes; ligands for PPARgamma inhibited the proliferation of normal and psoriatic human keratinocytes in culture. Troglitazone treatment normalized the histological features of psoriatic skin in organ culture and reduced the epidermal hyperplasia of psoriasis in the severe combined immunodeficient mouse and human skin transplant model of psoriasis (P<.05 compared with untreated controls). CONCLUSIONS: Peroxisome proliferator-activated receptor-gamma might be a useful intracellular target for the treatment of psoriasis; further study is needed to assess the clinical value of ligands for PPARgamma, including troglitazone.

OBJECTIVE: Recent studies suggest that air pollution plays a role in type 2 diabetes (T2D) incidence and mortality. The underlying physiological mechanisms have yet to be established. We hypothesized that air pollution adversely affects insulin sensitivity and secretion and serum lipid levels. RESEARCH DESIGN AND METHODS: Participants were selected from BetaGene (n = 1,023), a study of insulin resistance and pancreatic β-cell function in Mexican Americans. All participants underwent DXA and oral and intravenous glucose tolerance tests and completed dietary and physical activity questionnaires. Ambient air pollutant concentrations (NO2, O3, and PM2.5) for short- and long-term periods were assigned by spatial interpolation (maximum interpolation radius of 50 km) of data from air quality monitors. Traffic-related air pollution from freeways (TRAP) was estimated using the dispersion model as NOx. Variance component models were used to analyze individual and multiple air pollutant associations with metabolic traits. RESULTS: Short-term (up to 58 days cumulative lagged averages) exposure to PM2.5 was associated with lower insulin sensitivity and HDL-to-LDL cholesterol ratio and higher fasting glucose and insulin, HOMA-IR, total cholesterol, and LDL cholesterol (LDL-C) (all P ≤ 0.036). Annual average PM2.5 was associated with higher fasting glucose, HOMA-IR, and LDL-C (P ≤ 0.043). The effects of short-term PM2.5 exposure on insulin sensitivity were largest among obese participants. No statistically significant associations were found between TRAP and metabolic outcomes. CONCLUSIONS: Exposure to ambient air pollutants adversely affects glucose tolerance, insulin sensitivity, and blood lipid concentrations. Our findings suggest that ambient air pollutants may contribute to the pathophysiology in the development of T2D and related sequelae.

Residents of the area now occupied by the southwestern United States and northwestern Mexico have had to deal with coccidioidomycosis and complicating meningitis for >1500 years. The hundredth anniversary of the reporting of disseminated coccidioidomycosis has just passed. This year has the dubious distinction of being the hundredth anniversary of the first description of coccidioidal meningitis. Although intrathecal amphotericin B began to be used for therapy 50 years ago, and although we have benefited from azole therapy for >10 years, the morbidity and mortality associated with this all-too-common disease remain unacceptably high. This review will endeavor to discuss the pathogenic, pathophysiologic, clinical, laboratory, radiologic, and therapeutic features of meningitis secondary to Coccidioides infection.

RATIONALE: Asthma and obesity often occur together in children. It is unknown whether asthma contributes to the childhood obesity epidemic. OBJECTIVES: We aimed to investigate the effects of asthma and asthma medication use on the development of childhood obesity. METHODS: The primary analysis was conducted among 2,171 nonobese children who were 5-8 years of age at study enrollment in the Southern California Children's Health Study (CHS) and were followed for up to 10 years. A replication analysis was performed in an independent sample of 2,684 CHS children followed from a mean age of 9.7 to 17.8 years. MEASUREMENTS AND MAIN RESULTS: Height and weight were measured annually to classify children into normal, overweight, and obese categories. Asthma status was ascertained by parent- or self-reported physician-diagnosed asthma. Cox proportional hazards models were fitted to assess associations of asthma history with obesity incidence during follow-up. We found that children with a diagnosis of asthma at cohort entry were at 51% increased risk of developing obesity during childhood and adolescence compared with children without asthma at baseline (hazard ratio, 1.51; 95% confidence interval, 1.08-2.10) after adjusting for confounders. Use of asthma rescue medications at cohort entry reduced the risk of developing obesity (hazard ratio, 0.57; 95% confidence interval, 0.33-0.96). In addition, the significant association between a history of asthma and an increased risk of developing obesity was replicated in an independent CHS sample. CONCLUSIONS: Children with asthma may be at higher risk of obesity. Asthma rescue medication use appeared to reduce obesity risk independent of physical activity.

OBJECTIVE: Family communication is important for delivering high quality end-of-life care in the intensive care unit, yet little research has been conducted to describe and evaluate clinician-family communication with non-English-speaking family members. We assessed clinician-family communication during intensive care unit family conferences involving interpreters and compared it with conferences without interpreters. DESIGN: Cross-sectional descriptive study. SETTING: Family conferences in the intensive care units of four hospitals during which discussions about withdrawing life support or delivery of bad news were likely to occur. PARTICIPANTS: Seventy family members from ten interpreted conferences and 214 family members from 51 noninterpreted conferences. Nine different physicians led interpreted conferences and 36 different physicians led noninterpreted conferences. MEASUREMENTS: All 61 conferences were audiotaped. We measured the duration of the time that families, interpreters, and clinicians spoke during the conference, and we tallied the number of supportive statements issued by clinicians in each conference. RESULTS: The mean conference time was 26.3 +/- 13 mins for interpreted and 32 +/- 15 mins for noninterpreted conferences (p = 0.25). The duration of clinician speech was 10.9 +/- 5.8 mins for interpreted conferences and 19.6 +/- 10.2 mins for noninterpreted conferences (p = 0.001). The amount of clinician speech as a proportion of total speech time was 42.7% in interpreted conferences and 60.5% in noninterpreted conferences (p = 0.004). Interpreter speech accounted for 7.9 +/- 4.4 mins and 32% of speech in interpreter conferences. Interpreted conferences contained fewer clinician statements providing support for families, including valuing families' input (p = 0.01), easing emotional burdens (p < 0.01), and active listening (p < 0.01). CONCLUSIONS: This study suggests that families with non-English-speaking members may be at increased risk of receiving less information about their loved one's critical illness as well as less emotional support from their clinicians. Future studies should identify ways to improve communication with, and support for, non-English-speaking families of critically ill patients.

Journal Article Coccidioidomycosis: New Aspects of Epidemiology and Therapy Get access Hans E. Einstein, Hans E. Einstein From the Departments of Medicine, Bakersfield Memorial Hospital and Kern Medical Center, Bakersfield; and the USC and UCLA Schools of Medicine, Los Angeles, California Reprints or correspondence: Dr. Hans E. Einstein, Medical Staff Office, Bakersfield Memorial Hospital, 430 34th Street, Bakersfield, California 93301. Search for other works by this author on: Oxford Academic PubMed Google Scholar Royce H. Johnson Royce H. Johnson From the Departments of Medicine, Bakersfield Memorial Hospital and Kern Medical Center, Bakersfield; and the USC and UCLA Schools of Medicine, Los Angeles, California Search for other works by this author on: Oxford Academic PubMed Google Scholar Clinical Infectious Diseases, Volume 16, Issue 3, March 1993, Pages 349–356, https://doi.org/10.1093/clind/16.3.349 Published: 01 March 1993 Article history Received: 24 November 1992 Published: 01 March 1993

Bruton's tyrosine kinase (BTK) is crucial for FcεRI-mediated mast cell activation and essential for autoantibody production by B cells in chronic spontaneous urticaria (CSU). Fenebrutinib, an orally administered, potent, highly selective, reversible BTK inhibitor, may be effective in CSU. This double-blind, placebo-controlled, phase 2 trial (EudraCT ID 2016-004624-35 ) randomized 93 adults with antihistamine-refractory CSU to 50 mg daily, 150 mg daily and 200 mg twice daily of fenebrutinib or placebo for 8 weeks. The primary end point was change from baseline in urticaria activity score over 7 d (UAS7) at week 8. Secondary end points were the change from baseline in UAS7 at week 4 and the proportion of patients well-controlled (UAS7 ≤ 6) at week 8. Fenebrutinib efficacy in patients with type IIb autoimmunity and effects on IgG-anti-FcεRI were exploratory end points. Safety was also evaluated. The primary end point was met, with dose-dependent improvements in UAS7 at week 8 occurring at 200 mg twice daily and 150 mg daily, but not at 50 mg daily of fenebrutinib versus placebo. Asymptomatic, reversible grade 2 and 3 liver transaminase elevations occurred in the fenebrutinib 150 mg daily and 200 mg twice daily groups (2 patients each). Fenebrutinib diminished disease activity in patients with antihistamine-refractory CSU, including more patients with refractory type IIb autoimmunity. These results support the potential use of BTK inhibition in antihistamine-refractory CSU.

The Morel-Lavallée lesion is a closed soft-tissue degloving injury commonly associated with high-energy trauma. The thigh, hip, and pelvic region are the most commonly affected locations. Timely identification and management of a Morel-Lavallée lesion is crucial because distracting injuries in the polytraumatized patient can result in a missed or delayed diagnosis. Bacterial colonization of these closed soft-tissue injuries has resulted in their association with high rates of perioperative infection. Recently, MRI has been used to characterize and classify these lesions. Definitive management is dictated by the size, location, and age of the injury and ranges from percutaneous drainage to open débridement and irrigation. Chronic lesions may lead to the development of pseudocysts and contour deformities of the extremity.

BACKGROUND: The long-term success of coronary bypass surgery is dependent on graft patency after surgery. This trial was designed to determine if aspirin improved saphenous vein graft or internal mammary artery (IMA) graft patency between 1 and 3 years after coronary artery bypass grafting (CABG). METHODS AND RESULTS: After receiving aspirin 325 mg/d for 1 year after CABG and undergoing a 1-year postoperative cardiac catheterization, patients were randomized to receive either aspirin (325 mg) or placebo for 2 additional years. Angiography was performed 3 years after surgery to determine the primary end point-saphenous vein graft patency in 288 patients and IMA graft patency in 167 patients. At 3 years after CABG, the saphenous vein graft occlusion rate was 17.0% (62 of 365) for patients treated with aspirin compared with 19.7% (74 of 376) for those who received placebo (P = .404). For saphenous vein grafts that were patent at 1 year, the occlusion rate at 3 years was 4.8% (15 of 313) for patients treated with aspirin compared with 4.2% (13 of 310) for patients who received placebo (P = .757). At 3 years, the IMA graft occlusion rate was 10.3% (8 of 78) for patients treated with aspirin compared with 7.9% (7 of 89) for patients who received placebo (P = .594). For IMA grafts that were patent at 1 year, the occlusion rate was 4.3% (3 of 70) for patients treated with aspirin compared with 2.5% (2 of 81) for patients who received placebo (P = .541). CONCLUSIONS: These data suggest that aspirin treatment does not improve saphenous vein graft or IMA graft patency between 1 and 3 years after CABG.