Influence of Malaria Infection on the Elaboration of Soluble Mediators by Adherent Mononuclear Cells

MALARIA RESULTS IN TWO SEEMINGLY PARADOXICAL PERTURBATIONS OF THE IMMUNE RESPONSE: polyclonal B-cell activation and immunosuppression. To determine what immunoregulatory role mediators secreted by adherent cells might play in these alterations, we cultured adherent cells from uninfected mice and from mice at different times during infection with Plasmodium berghei or P. yoelii. Culture supernatants obtained from these cells were tested for their ability to enhance the in vitro proliferative responses of thymocytes to suboptimal concentrations of concanavalin A or to inhibit the mitogen-stimulated proliferation of normal spleen cells. Supernatants obtained from adherent cells of mice early in infection (days 1 to 3) contained significantly elevated levels of enhancing activity which on Bio-Gel P-100 chromatography resembled lymphocyte-activating factor. Later in infection (days 4 and 5), these supernatants contained inhibitory activity. Normal adherent cells, when cocultivated in vitro with parasitized erythrocytes, ingested parasite debris and were stimulated to produce the enhancing factor. At high parasite/adherent-cell ratios, cells elaborated an inhibitory factor. These findings suggest that during malaria, adherent cells are converted from a nonspecific helper role to a nonspecific suppressor role. This modulation in function may be due to the direct interaction between adherent cells and parasitized erythrocytes.     

Prospective evaluation of the Gen-Probe assay for detection of Legionellae in respiratory specimens

A prospective evaluation of a DNA probe assay for detection ofLegionella species was performed on 427 consecutive respiratory specimens submitted over an 18-month period. The Gen-Probe assay utilizing both low (4.0) and high (>7.0) ratio threshold values was compared to direct fluorescent antibody staining (DFA) as a predictor of isolation ofLegionella on culture. The highest sensitivity (63 %) was obtained with the lower threshold ratio, but was not significantly different from the result obtained with a threshold ratio of >7.0 (50 %, p=0.722) or DFA results (44 %, p=0.479). The specificity of the DNA probe assay was improved with the high threshold (99 %) compared either to the low threshold ratio (95 %, p=0.0002) or DFA (97 %, p=0.055). When the DNA probe was compared to DFA and/orLegionella isolation on culture, a significantly lower specificity (97 % versus 99 %, p=0.0006) and higher sensitivity (74 % versus 37 %, p=0.013) was obtained with a threshold value of 4.0 than >7.0. Ten of 20 specimens with a DNA probe ratio between 4.0 and 7.0 were DFA positive, although only two were isolated on culture. The DFA assay and both probe threshold ratios have a high negative predictive value when compared to culture. However, only the threshold ratio of >7.0 has a sufficiently high positive predictive value to be useful alone. Although the DNA probe appears to be a practical alternative to DFA testing for the rapid diagnosis ofLegionella infections, false-negative results emphasize the importance of obtaining several specimens for testing, and confirm the fundamental role of culture in the diagnosis ofLegionella infections.     

Immunohistochemical detection of c-erbB-2 protein in human benign and neoplastic prostate.

Both the polyclonal anti-c-erbB-2 peptide antiserum pAB 60 and the monoclonal anti-c-erbB-2 protein antibody mAB-1 detect the c-erbB-2 protein in human breast adenocarcinomas. We investigated c-erbB-2 expression in adult human benign hyperplastic and neoplastic prostates, using the avidin-biotin complex immunoperoxidase method. Formalin-fixed, paraffin-embedded specimens of benign hyperplastic prostate (13), prostatic adenocarcinoma (22), and prostatic adenocarcinoma lymph node metastases (two) were tested with pAB 60. Ten formalin-fixed, paraffin-embedded specimens of prostate adenocarcinoma, 11 frozen sections of benign hyperplastic specimens, and eight frozen sections of prostate adenocarcinoma were tested with mAB-1. Our results demonstrated consistent detection of c-erbB-2 immunohistochemically in frozen sections of both benign and malignant prostate. Preincubation of pAB 60 with the immunizing peptide blocked subsequent reactivity with prostatic tumor tissue, indicating specificity. However, fixation and processing protocols significantly affected the reactivity of the antigenic determinants detected by these antibodies, as mAB-1 was nonreactive with formalin-fixed, paraffin-embedded prostatic tissues. Differential reactivity of pAB 60 with malignant rather than benign glands was maximized by exposure of the specimen to the antibody at 4 degrees C rather than 22 degrees C. The most frequently observed staining pattern with both antibodies was cytoplasmic. However, mAB-1 produced distinctly membranous staining in two frozen specimens of benign hyperplasia and one specimen of prostate cancer.     

Comparing standard care with a physician and pharmacist team approach for uncontrolled hypertension

OBJECTIVE: To assess the effect of a physician and pharmacist teamwork approach to uncontrolled hypertension in a medical resident teaching clinic, for patients who failed to meet the recommended goals of the fifth Joint National Commission on Detection, Evaluation and Treatment of High Blood Pressure. HYPOTHESIS: Physician and pharmacist teamwork can improve the rate of meeting national blood pressure goals in patients with previously uncontrolled hypertension. DESIGN: A single-blinded randomized controlled trial lasting 6 months. SETTING: A primary care outpatient teaching clinic. PATIENTS: A sample of 95 adult hypertensive patients who failed to meet national blood pressure goals based on three consecutive visits over a 6-month period. INTERVENTION: Patients were randomly assigned to a control arm of standard medical care or to an intervention arm in which a physician and pharmacist worked together as a team. MAIN RESULTS: At study completion, the percentage of patients achieving national goals due to intervention was more than double the percentage in the control arm (55% vs 20%, p < .001). Systolic blood pressure declined 23 mm Hg in the intervention arm versus 11 mm Hg in the control arm (p < .01). Diastolic blood pressure declined 14 and 3 mm Hg in the intervention and control arms, respectively (p < .001). The intervention worked equally as well in men and women and demonstrated noticeable promise in a minority of mixed-ancestry Hawaiians in whom hypertension is of special concern. CONCLUSIONS: Patients who fail to achieve national blood pressure goals under standard outpatient medical care may benefit from a program that includes a physician and pharmacist teamwork approach. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Queen’s Medical Center. This work was supported by a grant from the Queen’s Medical Center, Honolulu, Hawaii and by a Research Centers in Minorities Institutions Award (P20 RR 11091) from the National Institutes of Health.     

Dynamic Three-Dimensional Ultrasound to Evaluate Scapular Movement Among Manual Wheelchair Users and Healthy Controls

Background:

A large percentage of individuals with spinal cord injury (SCI) report shoulder pain that can limit independence and quality of life. The pain is likely related to the demands placed on the shoulder by transfers and propulsion. Shoulder pathology has been linked to altered scapular mechanics; however, current methods to evaluate scapular movement are invasive, require ionizing radiation, are subject to skin-based motion artifacts, or require static postures.

Objective:

To investigate the feasibility of applying 3-dimensional ultrasound methods, previously used to look at scapular position in static postures, to evaluate dynamic scapular movement.

Method:

This study evaluated the feasibility of the novel application of a method combining 2-dimensional ultrasound and a motion capture system to determine 3-dimensional scapular position during dynamic arm elevation in the scapular plane with and without loading.

Results:

Incremental increases in scapular rotations were noted for extracted angles of 30°, 45°, 60°, and 75° of humeral elevation. Group differences were evaluated between a group of 16 manual wheelchair users (MWUs) and a group of age- and gender-matched able-bodied controls. MWUs had greater scapular external rotation and baseline pathology on clinical exam. MWUs also had greater anterior tilting, with this difference further accentuated during loading. The relationship between demographics and scapular positioning was also investigated, revealing that increased age, pathology on clinical exam, years since injury, and body mass index were correlated with scapular rotations associated with impingement (internal rotation, downward rotation, and anterior tilting).

Conclusion:

Individuals with SCI, as well as other populations who are susceptible to shoulder pathology, may benefit from the application of this imaging modality to quantitatively evaluate scapular positioning and effectively target therapeutic interventions.Key words: kinematics, scapula, ultrasound, wheelchair userThe shoulder is a common site of injury across many populations. Because it is the most mobile joint in the body, the high prevalence of disorders is not surprising. Individuals are at increased risk for shoulder pathology when exposed to high forces, sustained postures, and repetitive movements.¹ Wheelchair users are exposed to all of these factors in activities of daily living. Among manual wheelchair users (MWUs), 35% to 67% report shoulder pain.^2–7 In this population, the presence of shoulder dysfunction significantly affects function and decreases quality of life.^8,9 With altered scapular kinematics being linked to a multitude of shoulder problems, the identification of changes in kinematics may allow for earlier detection of pathology and targeting of appropriate interventions.^10–25 However, evaluation of dynamic scapular movement is a challenging task, as the scapula rotates about 3 axes while also gliding underneath overlying tissue. Direct visualization of the bone is ideal but is often limited by cost, availability, and exposure to radiation, and skin-based systems are prone to error.^26–33The overall goal of this study was to investigate the feasibility of applying 3-dimensional ultrasound methods, previously used to look at scapular position in static postures, to evaluate dynamic scapular movement.³⁴ The specific goals were as follows:

1. Evaluate intermediate angles of functional elevation during dynamic movement (30°, 45°, 60°, and 75°). We hypothesize that we will see incremental increases in external rotation, upward rotation, and posterior tipping throughout the movement to maintain the distance between the acromion and humerus.
2. Compare dynamic scapular movement between MWUs and able-bodied controls (ABs). We anticipate that the nature of wheelchair propulsion and demands of activities of daily living will elucidate differences between this population and ABs with comparably lower daily demands on the shoulder.
3. Evaluate the effect of loading on scapular movement, as other studies have suggested that differences in kinematics are clearer in the presence of loading.^10,35,36
4. Investigate the relationship between shoulder pathology, age, years since injury, and body mass index (BMI) and scapular positioning.

     

Thirty-Day Post-Discharge Outcomes Following COVID-19 Infection

BackgroundThe clinical course of COVID-19 includes multiple disease phases. Data describing post-hospital discharge outcomes may provide insight into disease course. Studies describing post-hospitalization outcomes of adults following COVID-19 infection are limited to electronic medical record review, which may underestimate the incidence of outcomes.ObjectiveTo determine 30-day post-hospitalization outcomes following COVID-19 infection.DesignRetrospective cohort studySettingQuaternary referral hospital and community hospital in New York City.ParticipantsCOVID-19 infected patients discharged alive from the emergency department (ED) or hospital between March 3 and May 15, 2020.MeasurementOutcomes included return to an ED, re-hospitalization, and mortality within 30 days of hospital discharge.ResultsThirty-day follow-up data were successfully collected on 94.6% of eligible patients. Among 1344 patients, 16.5% returned to an ED, 9.8% were re-hospitalized, and 2.4% died. Among patients who returned to the ED, 50.0% (108/216) went to a different hospital from the hospital of the index presentation, and 61.1% (132/216) of those who returned were re-hospitalized. In Cox models adjusted for variables selected using the lasso method, age (HR 1.01 per year [95% CI 1.00–1.02]), diabetes (1.54 [1.06–2.23]), and the need for inpatient dialysis (3.78 [2.23–6.43]) during the index presentation were independently associated with a higher re-hospitalization rate. Older age (HR 1.08 [1.05–1.11]) and Asian race (2.89 [1.27–6.61]) were significantly associated with mortality.ConclusionsAmong patients discharged alive following their index presentation for COVID-19, risk for returning to a hospital within 30 days of discharge was substantial. These patients merit close post-discharge follow-up to optimize outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-06924-0.KEY WORDS: COVID-19, mortality, re-admission, discharge     

Chronic suppression of insulin by diazoxide alters the activities of key enzymes regulating hepatic gluconeogenesis in Zucker rats

OBJECTIVES: Chronic attenuation of hyperinsulinemia by diazoxide (DZ), an inhibitor of glucose-mediated insulin secretion, improved insulin sensitivity and glucose tolerance and caused down-regulation of lipid metabolizing enzymes in adipose tissue and decreased the rate of weight gain in mildly hyperglycemic obese Zucker rats. Since the liver plays a central role in glucose homeostasis, we studied the effect of chronic insulin suppression on key insulin-sensitive enzymes regulating hepatic gluconeogenesis. METHODS: DZ (150 mg/kg per day) or vehicle (control) was administered to 7-week-old female obese and lean Zucker rats for a period of 4 weeks. RESULTS: DZ-treated animals showed lower fasting plasma insulin levels (P<0.001) than their controls. Plasma glucose levels were lower in DZ obese rats than in controls (P<0.001), without a significant change in DZ lean animals. DZ had no effect on glucose transporter 2 protein expression in either strain. DZ treatment resulted in lower hepatic glucokinase (P<0.001) and glucose-6-phosphatase (P<0.0001) and phosphoenolpyruvate carboxykinase (PEPCK) activities only in obese rats compared with controls (P<0.001). However, DZ-treated lean rats demonstrated higher PEPCK activity than controls (P<0.002). DZ-treated animals demonstrated enhanced hepatic glucose-6-phosphate content (P<0.01), glycogen synthase activity (P<0.0001) and glycogen content (P<0.02) compared with their controls despite increased hepatic glycogen phosphorylase a activity in these animals (P<0.02). CONCLUSIONS: Chronic suppression of hyperinsulinemia in obese Zucker rats by DZ decreased the activities of key enzymes regulating hepatic gluconeogenesis, implying that attenuation of the hyperinsulinemic state by DZ may be therapeutically beneficial.