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Biomedical subjects

M Shah

Publications and source records attributed to M Shah.

At least 55 records · Page 3Linked to original sources

Influenza virus infection induces metallothionein gene expression in the mouse liver and lung by overlapping but distinct molecular mechanisms.

Metallothionein I (MT-I) and MT-II have been implicated in the protection of cells against reactive oxygen species (ROS), heavy metals, and a variety of pathological and environmental stressors. Here, we show a robust increase in MT-I/MT-II mRNA level and MT proteins in the livers and lungs of C57BL/6 mice exposed to the influenza A/PR8 virus that infects the upper respiratory tract and lungs. Interleukin-6 (IL-6) had a pronounced effect on the induction of these genes in the liver but not the lung. Treatment of the animals with RU-486, a glucocorticoid receptor antagonist, inhibited induction of MT-I/MT-II in both liver and lung, revealing a direct role of glucocorticoid that is increased upon infection in this induction process. In vivo genomic footprinting (IVGF) analysis demonstrated involvement of almost all metal response elements, major late transcription factor/antioxidant response element (MLTF/ARE), the STAT3 binding site on the MT-I upstream promoter, and the glucocorticoid responsive element (GRE1), located upstream of the MT-II gene, in the induction process in the liver and lung. In the lung, inducible footprinting was also identified at a unique gamma interferon (IFN-gamma) response element (gamma-IRE) and at Sp1 sites. The mobility shift analysis showed activation of STAT3 and the glucocorticoid receptor in the liver and lung nuclear extracts, which was consistent with the IVGF data. Analysis of the newly synthesized mRNA for cytokines in the infected lung by real-time PCR showed a robust increase in the levels of IL-10 and IFN-gamma mRNA that can activate STAT3 and STAT1, respectively. A STAT1-containing complex that binds to the gamma-IRE in vitro was activated in the infected lung. No major change in MLTF/ARE DNA binding activity in the liver and lung occurred after infection. These results have demonstrated that MT-I and MT-II can be induced robustly in the liver and lung following experimental influenza virus infection by overlapping but distinct molecular mechanisms.

Animals↗

Detection of regional temporal abnormalities in left ventricular function during acute myocardial ischemia.

Echocardiographic diagnosis of myocardial ischemia is based on visualizing hypokinesis, which occurs late in the ischemic cascade. We hypothesized that temporal changes in endocardial motion may constitute sensitive early markers of ischemia. Two protocols were performed in 19 anesthetized pigs. Protocol 1 included 54 intracoronary balloon occlusions. Transthoracic images were acquired at baseline and every 15 s during 5 min of occlusion and reperfusion. In protocol 2, ischemia was induced in 12 animals by use of graded dobutamine infusion, after creating significant partial occlusions without a resting wall motion abnormality. Systolic and diastolic endocardial motion was color encoded using color kinesis and analyzed using custom software. All ischemic episodes caused detectable and reversible changes. The earliest sign of ischemia was tardokinesis in 31/54 occlusions, whereas hypokinesis appeared first in 23/54 cases. Dobutamine-induced ischemia caused tardokinesis first in 9/12 and hypokinesis in 3/12 animals. Reversible ischemic changes in regional left ventricular performance can be objectively detected using analysis of echocardiographic images and will likely improve the early noninvasive diagnosis of acute ischemia.

Animals↗

Treatment of ulnar impaction syndrome with the wafer procedure.

Our objective was to evaluate the efficacy of wafer resection of the distal ulna (the wafer procedure) as treatment for ulnar impaction syndrome. Between 1995 and 1997, 26 patients were surgically treated for refractory wrist pain secondary to ulnar impaction syndrome. The diagnosis was based on physical examination, radiologic imaging, and wrist arthroscopy, and confirmatory pathoanatomy was identified at the time of surgery in all cases. The study population consisted of 18 women and 8 men, and patient age averaged 42 years. Follow-up averaged 27 months (range, 17-41 months). Twenty-three patients were completely satisfied with pain relief and the functional status of their wrists at final follow-up. Range of motion returned to baseline in the majority of cases, usually by 3 months, and grip strength increased an average of 11 kg (P < or = .005). The wafer procedure is an effective treatment alternative to ulnar-shortening osteotomy for ulnar impaction syndrome and avoids the risk of nonunion and hardware-related complications.

Adult↗

Metastatic cervical cancer with unusual presentation: a case report.

Carcinoma of the cervix is rare in the United States thanks to widespread use of screening Pap smears. A 60-year-old female with right upper quadrant pain, diarrhea, and urinary incontinence was found to have stage IV B cervical cancer. Computerized tomography (CT) was of value in diagnosis. Like mammography, which improves survival by detecting malignant disease at an early stage, the Pap test is central in preventing the development of invasive cervical cancer.

Abdominal Pain↗

Pathophysiology and clinical spectrum of acute congestive heart failure.

This article reviews the current understanding of the pathophysiology and clinical spectrum of heart failure. A cascade of hemodynamic and neurohormonal derangements result from a decrease in ventricular performance or cardiac output. Because neurohormonal activation has become a target for intervention in heart failure, the role of selected systems (sympathetic nervous, renin-angiotensin-aldosterone) and of natriuretic peptides is detailed. The spectrum (from compensated to acute decompensated) within which congestive heart failure patients present is reviewed, with special attention paid to the intermediate, transitional group of patients, who pose unique diagnostic and therapeutic challenges. Given these variable presentations, there is an obligation to tailor therapy accordingly.

Atrial Natriuretic Factor↗

Development and initial evaluation of a culturally sensitive cholesterol-lowering diet program for Mexican and African American patients with systemic lupus erythematosus.

OBJECTIVE: To develop and evaluate acceptability of an intensive and ethnic-specific cholesterol-lowering diet program with a strong behavioral component in patients with systemic lupus erythematosus (SLE). METHOD: A comprehensive program with a behavioral component and culturally sensitive menus was developed in an effort to alter dietary behavior in patients with SLE. Four SLE patients, 2 African American and 2 Mexican American, enrolled in this program. Data on food intake (3-day food record), acceptability of the program (subjective response), and physiologic variables were collected at baseline, 6 weeks, and 12 weeks. RESULTS: The program was highly rated by all patients and found to be informative, easy to understand, ethnically sensitive, and to contain useful behavioral maintenance strategies. All 4 patients surpassed or were close to their diet goals at both 6 and 12 weeks. In this small group of patients, there was a statistically significant reduction in low-density lipoprotein cholesterol (P = 0.04) and body weight (P = 0.001), as assessed by repeated measures analysis of variance. CONCLUSION: The culturally specific cholesterol-reducing diet program was highly rated and appeared to be effective in changing the diet of this small group of SLE patients, as determined by their food records and body weight. The impact of this program, including the individual components on cardiovascular disease risk factors, needs to be evaluated in a larger multiple-arm study with a lengthier intervention.

Adult↗

Rapid removal of vancomycin by continuous veno-venous hemofiltration.

We describe a 14-year-old girl with staphylococcal (coagulase-negative) ventriculo-peritoneal shunt infection, who developed oliguric acute renal failure and was found to have a serum vancomycin concentration of 250 microg/ml. Since only about 10%-50% of vancomycin is bound to protein in blood, we employed continuous veno-venous hemofiltration (CVVH) with a high ultrafiltration rate (1,800 ml/h) for increased convective clearance to remove vancomycin, which may have contributed to the acute renal failure. At the end of 38 h of CVVH, the vancomycin concentration had decreased in an exponential manner to 27 microg/ml. Over the subsequent 3-4 days, her renal function improved and the vancomycin concentration decreased further to <5 microg/ml. In conclusion, we believe that a high serum vancomycin concentration may be nephrotoxic and demonstrate that CVVH can be used effectively to remove vancomycin in children with acute renal failure.

Acute Kidney Injury↗

Does gender bias exist in the medical management of heart failure?

INTRODUCTION: The purpose of this study was to ascertain the presence of gender bias in the medical management of heart failure, and to assess its association with the specialty of the caregiver physician. METHODS: In 309 patients with documented left ventricular systolic dysfunction (ejection fraction <45%) and at least one hospitalization for heart failure, we assessed the frequency of use of effective medical therapy for heart failure among male (n=187) and female (n=122) patients at the time of hospital discharge. We constructed multivariate models relating patient gender and caregiver specialty to utilization of each class of medications (angiotensin-converting enzyme inhibitors, effective vasodilator therapy (i.e., angiotensin-converting enzyme inhibitors or hydralazine-nitrate therapy), diuretics, digoxin), and combination therapy (i.e., vasodilator plus diuretic plus digoxin). RESULTS: In crude analyses, we did not find any difference in utilization of medications between male and female patients. Multivariate analyses involving adjustment for age, race, coronary artery disease, ejection fraction, and other relevant variables, revealed higher utilization of combination therapy by cardiologists in male versus female patients (adjusted odds ratios=2.07; 95%CI=1.09-3.95), and higher utilization of digoxin therapy by non-cardiologists in female versus male patients (adjusted odds ratio=5.5; 95%CI=1.4-22.2). No gender or caregiver specialty differences were seen in models relating to the other classes of medications. CONCLUSIONS: Our findings suggest the presence of gender bias in the medical management of heart failure, and identify an interesting interaction between caregiver specialty and gender bias.

Aged↗

Balloon-expandable stent placement for superior vena cava-right atrial stenosis after heart transplantation.

Anastomotic Stenoses are well known as a complication of vascular and cardiovascular surgical procedures; such a lesion was encountered at the superior vena cava-right atrial anastomosis after cardiac transplantation. A balloon expandable stent was used to relieve this anastomotic constriction, employing a 16 mm diameter balloon to deliver a P304 stent. Stent placement resulted in complete relief of the patient's symptoms and facilitated the passage of bioptomes through the superior vena cava for subsequent biopsy procedures following cardiac transplantation.

Anastomosis, Surgical↗

The pharmacology of hSK1 Ca2+-activated K+ channels expressed in mammalian cell lines.

The pharmacology of hSK1, a small conductance calcium-activated potassium channel, was studied in mammalian cell lines (HEK293 and COS-7). In these cell types, hSK1 forms an apamin-sensitive channel with an IC(50) for apamin of 8 nM in HEK293 cells and 12 nM in COS-7 cells. The currents in HEK293 cells were also sensitive to tubocurarine (IC(50)=23 microM), dequalinium (IC(50)=0.4 microM), and the novel dequalinium analogue, UCL1848 (IC(50)=1 nM). These results are very different from the pharmacology of hSK1 channels expressed in Xenopus oocytes and suggest the properties of the channel may depend on the expression system. Our findings also raise questions about the role of SK1 channels in generating the apamin-insensitive slow afterhyperpolarization observed in central neurones.

Animals↗

Contact sensitivity to nickel and other metals in jewelry reactors.

BACKGROUND: Many patients who give a history of a dermatitis reaction to jewelry or metal contact with skin are negative to metals on standard patch testing. Some may be showing false-negative reactions. OBJECTIVE: Our purpose was to determine whether patients with a history of jewelry reactions but whose standard patch tests were negative have a false-negative reaction or are allergic to metals other than nickel, cobalt, or chromium. METHODS: Four hundred forty-nine patients were studied who gave a history of reacting to jewelry or metal. Of these, 210 were tested to the metals in the European standard series (ie, nickel, cobalt, and chromate), and 239 were tested to the metals in the standard series and to an extended metal series of palladium, gold, platinum, a second nickel salt, and a nickel/cobalt mixture. These were compared with 752 patients who did not give a history of jewelry or metal reactions, of which 50, besides the standard series, were also treated with the additional metal series. RESULTS: A higher proportion of jewelry-reactive patients tested with the extended series reacted to nickel (and to other metals) than those who were tested only with the European standard series: (61% vs 38%; P <.0001 ). The use of the extended series showed that palladium allergy was common, present in 34% of nickel-allergic patients, but it always occurred with nickel sensitivity. Gold allergy coexisted with nickel sensitivity in 10% of cases. Testing simultaneously with separate patches containing 5% nickel sulfate and 5% nickel chloride showed a concordance of 71% in identified nickel-sensitive patients. Nickel sulfate was more likely than nickel chloride to detect nickel sensitivity. The use of a combined preparation of 2.5% nickel sulfate and 0.5% cobalt chloride in petrolatum revealed only 3 jewelry-reactive patients who were negative to other metals. There was a slightly higher proportion of atopic patients in the patch test-negative jewelry reactors group than in the positive group; however, the difference was not significant and it was not sufficient to account for the negative findings. CONCLUSION: Some jewelry reactors who had negative patch tests are likely to be subclinically allergic to nickel. We suggest that the higher number of antigens, or perhaps the larger nickel load, in the extended metal series, resulted in a larger proportion of patients reacting. To better demonstrate nickel allergy in jewelry reactors, patients should be patch tested to a metal series that contains palladium and gold salts and perhaps a second nickel patch because these may reveal the presence of nickel sensitivity when standard patch tests would otherwise have been negative.

Chromium↗

Impact of hypoxemia on the performance of cerebral oximeter in volunteer subjects.

Adverse neurological events during hypoxic episodes in high-risk patients or in patients not thought to be at risk while undergoing procedures increase morbidity and mortality. The ability to reliably monitor cerebral oxygenation could serve as an indicator for the need of therapeutic intervention and it's overall effect. This study was designed to verify the reliability of the only commercially available continuous noninvasive monitor, the INVOS 3100 (Somanetics Corp., Troy, MI), in subjects with varying levels of hypoxemia. Six adult volunteer subjects were enrolled. After placement of electrocardiogram (EKG), noninvasive blood pressure (NIBP), pulse oximeter (SpO2), cerebral oximeter (rSO2), a 20 g radial artery catheter, and a 4 F oximetric jugular bulb catheter, the subjects were given hypoxic mixtures to breathe to varying levels of desaturation. Arterial and mixed venous blood was drawn for blood-gas analysis at each level of O2 saturation. The cerebral hemoglobin saturation value from the cerebral oximeter was compared to the combined brain saturation using the formula: estimated field saturation between the light source and the detector (fSO2) = 0.25 x the arterial oxygen saturation (SaO2) + 0.75 x the jugular bulb venous oxygen saturation (SjvO2), (fSO2 = 0.25 SaO2 + 0.75 SjvO2). Statistical analysis demonstrated a correlation of 0.67 between rSO2 and fSO2 and a bias of -3.1% with a precision of 12.1%. Minimal bias of 0.38% and precision of 6.22% were calculated for transitional error. We concluded from the study that rSO2 may serve as a reliable indicator of changes in brain oxygenation induced by hypoxemia.

Adult↗

Maturation of proximal straight tubule NaCl transport: role of thyroid hormone.

We have recently demonstrated that the rates of both active and passive proximal straight tubule (PST) NaCl transport in neonatal rabbits were less than in adults. In this segment NaCl entry across the apical membrane is via parallel Na(+)/H(+) and Cl(-)/OH(-) exchangers, which increases in activity with maturation. The present in vitro microperfusion study examined whether thyroid hormone plays a role in the maturational increase in PST NaCl transport. Neonatal and adult PST were perfused with a high-chloride-low bicarbonate solution without organic solutes, simulating late proximal tubule fluid. Thyroid hormone-treated neonates had a higher rate of PST total and passive NaCl transport. In 8-wk-old animals that were hypothyroid since birth, the maturational increase in total and passive NaCl transport was prevented. Thyroid treatment for 4 days in hypothyroid 8-wk-old rabbits increased the rate of both total and passive NaCl transport. The maturational increases in both Na(+)/H(+) and Cl(-)/OH(-) exchange activities were blunted in 8-wk-old hypothyroid animals and increased to control levels with thyroid treatment. This study demonstrates that thyroid hormone is a factor responsible for the maturational increase in both active and passive PST NaCl transport.

Aging↗

Ca(2+) channels involved in the generation of the slow afterhyperpolarization in cultured rat hippocampal pyramidal neurons.

The advantages of using isolated cells have led us to develop short-term cultures of hippocampal pyramidal cells, which retain many of the properties of cells in acute preparations and in particular the ability to generate afterhyperpolarizations after a train of action potentials. Using perforated-patch recordings, both medium and slow afterhyperpolarization currents (mI(AHP) and sI(AHP), respectively) could be obtained from pyramidal cells that were cultured for 8-15 days. The sI(AHP) demonstrated the kinetics and pharmacologic characteristics reported for pyramidal cells in slices. In addition to confirming the insensitivity to 100 nM apamin and 1 mM TEA, we have shown that the sI(AHP) is also insensitive to 100 nM charybdotoxin but is inhibited by 100 microM D-tubocurarine. Concentrations of nifedipine (10 microM) and nimodipine (3 microM) that maximally inhibit L-type calcium channels reduced the sI(AHP) by 30 and 50%, respectively. However, higher concentrations of nimodipine (10 microM) abolished the sI(AHP), which can be partially explained by an effect on action potentials. Both nifedipine and nimodipine at maximal concentrations were found to reduce the HVA calcium current in freshly dissociated neurons to the same extent. The N-type calcium channel inhibitor, omega-conotoxin GVIA (100 nM), irreversibly inhibited the sI(AHP) by 37%. Together, omega-conotoxin (100 nM) and nifedipine (10 microM) inhibited the sI(AHP) by 70%. 10 microM ryanodine also reduced the sI(AHP) by 30%, suggesting a role for calcium-induced calcium release. It is concluded that activation of the sI(AHP) in cultured hippocampal pyramidal cells is mediated by a rise in intracellular calcium involving multiple pathways and not just entry via L-type calcium channels.

Action Potentials↗

Novel amiloride-sensitive sodium-dependent proton secretion in the mouse proximal convoluted tubule.

The proximal convoluted tubule (PCT) reabsorbs most of the filtered bicarbonate. Proton secretion is believed to be mediated predominantly by an apical membrane Na(+)/H(+) exchanger (NHE). Several NHE isoforms have been cloned, but only NHE3 and NHE2 are known to be present on the apical membrane of the PCT. Here we examined apical membrane PCT sodium-dependent proton secretion of wild-type (NHE3(+/+)/NHE2(+/+)), NHE3(-/-), NHE2(-/-), and double-knockout NHE3(-/-)/NHE2(-/-) mice to determine their relative contribution to luminal proton secretion. NHE2(-/-) and wild-type mice had comparable rates of sodium-dependent proton secretion. Sodium-dependent proton secretion in NHE3(-/-) mice was approximately 50% that of wild-type mice. The residual sodium-dependent proton secretion was inhibited by 100 microM 5-(N-ethyl-N-isopropyl) amiloride (EIPA). Luminal sodium-dependent proton secretion was the same in NHE3(-/-)/NHE2(-/-) as in NHE3(-/-) mice. These data point to a previously unrecognized Na(+)-dependent EIPA-sensitive proton secretory mechanism in the proximal tubule that may play an important role in acid-base homeostasis.

Amiloride↗