Biomedical subjects

Zeenat Safdar

Publications and source records attributed to Zeenat Safdar.

6 recordsLinked to original sources

PubMed2025

Real-World Experience of Midodrine in Hospital Setting in Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH), a progressive disease, is characterized by increased pulmonary vascular resistance (PVR) and leads to right ventricular failure and premature death. PAH therapies aim to reduce PVR; however, these treatments as vasodilators may also result in reduced systemic vascular resistance and mean arterial pressure (MAP), leading to clinical or symptomatic hypotension. Low MAP can limit the administration of optimal dosage of PAH drugs. Midodrine, an oral alpha-1 adrenergic agonist, as a promising intervention, can potentially increase mean MAP and improve tolerance to PAH therapies. RESEARCH QUESTION: Does the use of midodrine improve MAP and allow for simultaneous uptitration of PAH therapy while hospitalized? STUDY DESIGN AND METHODS: A retrospective analysis of 433 patients treated at Houston Methodist Lung Center was undertaken between January 2005 and September 2022. Of these, 57 patients were prescribed midodrine during their hospital stay. We matched 57 patients 1:1 with propensity score matching between patients with PAH not given midodrine (control patients) based on age, sex, World Health Organization functional class, B-type natriuretic peptide, and 6-minute walk distance. RESULTS: Among hospitalized patients with PAH, those receiving midodrine were more likely to undergo uptitration of their PAH medications compared with those not receiving midodrine (n = 30 vs n = 17, respectively; P < .05). Patients on midodrine during hospitalization received higher doses of epoprostenol (P < .001), treprostinil (P < .05), and selexipag (P < .05). Additionally, no adverse effects attributable to midodrine were reported. INTERPRETATION: This study, to our knowledge the first large-scale analysis of PAH data, investigated the use of midodrine in hospitalized patients with PAH. In this single-center study, we share real-world experience of using midodrine to mitigate systemic hypotension, thereby facilitating the uptitration of PAH-targeted therapies.

B-type natriuretic peptide (BNP)↗

PubMed2005

Inhibition of acid-induced lung injury by hyperosmolar sucrose in rats.

RATIONALE: Acid aspiration causes acute lung injury (ALI). Recently, we showed that a brief intravascular infusion of hyperosmolar sucrose, given concurrently with airway acid instillation, effectively blocks the ensuing ALI. OBJECTIVES: The objective of the present study was to determine the extent to which intravascular infusion of hyperosmolar sucrose might protect against acid-induced ALI when given either before or after acid instillation. METHODS: Our studies were conducted in anesthetized rats and in isolated, blood-perfused rat lungs. We instilled HCl through the airway, and we quantified lung injury in terms of the extravascular lung water (EVLW) content, filtration coefficient (Kfc), and cell counts and protein concentration in the bronchoalveolar lavage. We infused hyperosmolar sucrose via the femoral vein. RESULTS: In anesthetized rats, airway HCl instillation induced ALI as indicated by a 52% increase of EVLW and a threefold increase in Kfc. However, a 15-min intravenous infusion of hyperosmolar sucrose given up to 1 h before or 30 min after acid instillation markedly blunted the increases in EVLW, as well as the increases in cell count, and in protein concentration in the bronchoalveolar lavage. Hyperosmolar pretreatment also blocked the acid-induced increase of Kfc. Studies in isolated perfused lungs indicated that the protective effect of hyperosmolar sucrose was leukocyte independent. CONCLUSIONS: We conclude that a brief period of vascular hyperosmolarity protects against acid-induced ALI when the infusion is administered shortly before, or shortly after, acid instillation in the airway. The potential applicability of hyperosmolar sucrose in therapy for ALI requires consideration.

Animals↗

PubMed2004

The predictors of outcome in immunocompetent patients with hematogenous candidiasis.

OBJECTIVE: Clinical parameters that predict outcome in non-immunosuppressed candidemic patients are not fully understood. METHODS: Eighty-one consecutive episodes of candidemia were retrospectively evaluated in 75 patients during 1998-2000. RESULTS: Infection due to Candida albicans was common (n = 30; 37%) followed by Candida glabrata (n = 25; 31%), Candida parapsilosis (n = 14; 17%), Candida tropicalis (n = 6; 7%), Candida krusei (n = 5; 6%), and Candida lusitaniae (n = 1; 1%). Among 70 evaluable patients, 31 (44%) had fungemia-associated mortality; advanced age (P < 0.004), underlying malignancy (P < 0.025), coronary artery disease (P < 0.01), and concurrent non-Candida species fungal infection (P < 0.047) were significant prognosticators of compromised short-term survival by multivariate analysis. Mortality was higher in patients with Candida glabrata (60%) and C. tropicalis (75%) infection compared to 44% deaths in individuals with C. albicans infection (P > 0.1). 11/25 (44%) of non-immunocompromised individuals died and 20/45 (44%) immunosuppressed patients succumbed to fungemia: persistent vs. non-persistent (< 3 days) Candida bloodstream invasion, neutropenia, diabetes mellitus, renal insufficiency, prior antimicrobial therapy, cirrhosis of liver, abdomino-pelvis surgery, and critical-care-unit vs. non critical-care-unit admission did not significantly impact outcome in either group. All 11 infants, including nine with prematurity, survived Candida species bloodstream infection (P < 0.025). CONCLUSIONS: Short-term mortality in candidemic non-immunocompromised patients was comparable to fungemia-associated deaths in immunosuppressed patients. Ischemic heart disease has appeared as a new predictor of unfavorable outcome in patients with hematogenous candidiasis.

Adolescent↗

PubMed2004

Cell-cell interactions in regulating lung function.

Tight junction barrier formation and gap junctional communication are two functions directly attributable to cell-cell contact sites. Epithelial and endothelial tight junctions are critical elements of the permeability barrier required to maintain discrete compartments in the lung. On the other hand, gap junctions enable a tissue to act as a cohesive unit by permitting metabolic coupling and enabling the direct transmission of small cytosolic signaling molecules from one cell to another. These components do not act in isolation since other junctional elements, such as adherens junctions, help regulate barrier function and gap junctional communication. Some fundamental elements related to regulation of pulmonary barrier function and gap junctional communication were presented in a Featured Topic session at the 2004 Experimental Biology Conference in Washington, DC, and are reviewed in this summary.

Animals↗

PubMed2003

Hyperosmolarity enhances the lung capillary barrier.

Although capillary barrier deterioration underlies major inflammatory lung pathology, barrier-enhancing strategies are not available. To consider hyperosmolar therapy as a possible strategy, we gave 15-minute infusions of hyperosmolar sucrose in lung venular capillaries imaged in real time. Surprisingly, this treatment enhanced the capillary barrier, as indicated by quantification of the capillary hydraulic conductivity. The barrier enhancement was sufficient to block the injurious effects of thrombin, TNF-alpha, and H2O2 in single capillaries, and of intratracheal acid instillation in the whole lung. Capillary immunofluorescence indicated that the hyperosmolar infusion markedly augmented actin filament formation and E-cadherin expression at the endothelial cell periphery. The actin-depolymerizing agent latrunculin B abrogated the hyperosmolar barrier enhancement as well as the actin filament formation, suggesting a role for actin in the barrier response. Furthermore, hyperosmolar infusion blocked TNF-alpha-induced P-selectin expression in an actin-dependent manner. Our results provide the first evidence to our knowledge that in lung capillaries, hyperosmolarity remodels the endothelial barrier and the actin cytoskeleton to enhance barrier properties and block proinflammatory secretory processes. Hyperosmolar therapy may be beneficial in lung inflammatory disease.

Actins↗

PubMedDate not supplied

Emergent bullectomy for acute respiratory failure in Ehlers-Danlos syndrome.

A 49-year-old man with Ehlers-Danlos syndrome developed acute respiratory failure requiring mechanical ventilation. Chest computed tomography demonstrated giant right bulla extending into the contralateral hemithorax with mediastinal shift. Surgical bullectomy with pleurodesis relieved tension effects and allowed weaning.

Acute Disease↗