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Biomedical subjects

D Sacks

Publications and source records attributed to D Sacks.

At least 37 records · Page 2Linked to original sources
PubMed1999

Dialysis graft declotting with very low dose urokinase: is it feasible to use "less and wait?".

PURPOSE: "Lyse and wait" dialysis graft declotting is simple and effective, but the minimum necessary dose of urokinase is unknown. The efficacy of the technique with very low dose urokinase is evaluated. MATERIALS AND METHODS: Twenty-one grafts in 17 patients were declotted with use of the lyse and wait technique, but with 5,000-15,000 U of urokinase initially. Graft angiography was performed when an interventional suite was available. Declotting was completed in the manner chosen by the individual operator. Angiograms, interventional radiology records, and dialysis records were reviewed. RESULTS: Technical and clinical success were achieved in 95% of cases. Mean initial urokinase dose was 6,667 U. Initial angiography was performed at a mean 86 minutes. Two cases required second 5,000-U boluses to achieve complete graft thrombolysis. In all other cases, complete or near complete graft thrombolysis was observed with the initial very low dose. No bleeding, arterial embolic, or pulmonary embolic complications were observed. CONCLUSIONS: Doses of urokinase as low as 5,000 U are effective for lyse and wait declotting. A substantial reduction in drug costs can be expected with the "less and wait" modification. Bleeding risk may also be reduced.

Adult↗
PubMed1999

Evidence that the high incidence of treatment failures in Indian kala-azar is due to the emergence of antimony-resistant strains of Leishmania donovani.

The possibility that the high frequency of treatment failures in Indian kala-azar might be due to infection with antimony-resistant strains of Leishmania donovani has not been experimentally addressed. L. donovani isolates were obtained from splenic aspiration smears of 24 patients in Bihar, India, who either did not respond (15) or did respond (9) to 1 or more full courses of treatment with sodium antimony gluconate (SAG). A strong correlation (P<.001) between clinical response and SAG sensitivity in vitro was observed only when strains were assayed as intracellular amastigotes: responsive isolates ED50=2.4+/-2.6, ED90=6.4+/-7.8 microgram SAG/mL; unresponsive isolates ED50=7.4+/-3.7 microgram SAG/mL, ED90=29.1+/-11.1 SAG/mL. No correlation with clinical response was found by use of extracellular promastigotes (ED50=48+/-22 vs. 52+/-29 microgram/mL). The emergence of antimony-resistant L. donovani strains appears to be a cause of treatment failures in India.

Adolescent↗
PubMed1998

Leishmania tropica: the identification and purification of metacyclic promastigotes and use in establishing mouse and hamster models of cutaneous and visceral disease.

Few experimental studies on Leishmania tropica have been undertaken despite the importance of this parasite as the cause of cutaneous leishmaniasis, and now visceral disease, in the Old World. In part, this is due to the absence of convenient animals models, especially mice, for L. tropica infections. An anti-lipophosphoglycan (LPG) monoclonal antibody XCIV 1H2-A8 (T11), specific for L. tropica, was found to distinguish between culture-derived procyclic and metacyclic promastigotes. The antibody was used to negatively select for nonagglutinated metacyclic forms in stationary cultures, and the exceptional virulence of the purified metacyclics was verified by their infectivity for mouse macrophages in vitro and by their ability to produce cutaneous lesions in footpads of BALB/c mice. The lesions produced by three cutaneous isolates of L. tropica were nonulcerative and nonprogressive. Nonetheless, the lesions failed to heal, and high numbers of parasites could be recovered from footpads and draining lymph nodes up to 9 months after infection. Infections using L. tropica metacyclics purified from cutaneous, visceral and viscerotropic (Desert Storm) isolates of L. tropica were compared in both mouse and hamster models. Differences in disease progression were found that may reflect the parasite tissue tropism and virulence displayed by these strains in their human hosts. These findings suggest a role for parasite-related determinants in the clinical spectrum of disease.

Agglutination Tests↗
PubMed1997

Reciprocal regulation of endothelial nitric-oxide synthase by Ca2+-calmodulin and caveolin.

The endothelial nitric-oxide synthase (eNOS) is a key determinant of vascular homeostasis. Like all known nitric-oxide synthases, eNOS enzyme activity is dependent on Ca2+-calmodulin. eNOS is dynamically targeted to specialized cell surface signal-transducing domains termed plasmalemmal caveolae and interacts with caveolin, an integral membrane protein that comprises a key structural component of caveolae. We have previously reported that the association between eNOS and caveolin is quantitative and tissue-specific (Feron, O., Belhassen, L., Kobzick, L., Smith, T. W., Kelly, R. A., and Michel, T. (1996) J. Biol. Chem. 271, 22810-22814). We now report that in endothelial cells the interaction between eNOS and caveolin is importantly regulated by Ca2+-calmodulin. Addition of calmodulin disrupts the heteromeric complex formed between eNOS and caveolin in a Ca2+-dependent fashion. In addition, overexpression of caveolin markedly attenuates eNOS enzyme activity, but this inhibition is reversed by purified calmodulin. Caveolin overexpression does not affect the activity of the other NOS isoforms, suggesting eNOS-specific inhibition of NO synthase by caveolin. We propose a model of reciprocal regulation of eNOS in endothelial cells wherein the inhibitory eNOS-caveolin complex is disrupted by binding of Ca2+-calmodulin to eNOS, leading to enzyme activation. These findings may have broad implications for the regulation of Ca2+-dependent signal transduction in plasmalemmal caveolae.

Animals↗
PubMed1995

Serum cardiac troponin T levels during treatment of early-stage breast cancer.

PURPOSE: To measure serum troponin T concentrations in patients with early-stage left breast cancer during breast-conserving radiation therapy. Troponin T has been introduced recently as a sensitive and specific marker for acute myocardial injury. PATIENTS AND METHODS: We compared pretreatment and posttreatment serum troponin T values in 50 patients undergoing radiation therapy to the entire left breast following conservative surgery for stage I and II breast cancer. RESULTS: No changes in troponin T concentrations were found after 45 to 46 Gy whole-breast irradiation. All women had undetectable or normal troponin T on the first and last day of treatment. There was no evidence of an upward trend during treatment. CONCLUSION: Radiation therapy to the left breast does not affect serum cardiac troponin T levels, despite the fact that a portion of the myocardium lies within the high-dose region. This suggests that the acute effects of radiation on the myocardium are minor. Long-term evaluation of these patients is necessary to rule out the possibility of late cardiac morbidity due to accelerated atherosclerosis. This study also suggests that an elevated troponin T level during or shortly after left breast irradiation should not be attributed to treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Effect of obesity on insulin resistance in normal subjects and patients with NIDDM.

Insulin resistance (IR) is a characteristic feature of non-insulin-dependent diabetes mellitus (NIDDM) as well as obesity, and a majority of NIDDM patients are obese. To assess the effect of obesity independent of NIDDM on IR, we studied the relationship between IR and obesity in 65 normal and 58 NIDDM subjects; we used body mass index (BMI) as a measure of obesity and glucose infusion rate (GINF) during a euglycemic hyperinsulinemic (120 mU.m-2.min-1) glucose clamp as a measure of IR. In lean normal subjects, GINF was 57.7 +/- 2.2 mumol.kg-1.min-1 (10.4 +/- 0.4 mg.kg-1.min-1) and the lean NIDDM subjects were markedly insulin-resistant, with a GINF of 34.4 +/- 2.8 mumol.kg-1.min-1 (6.2 +/- 0.5 mg.kg-1.min-1). Obese normal subjects were also insulin-resistant compared with lean normal subjects, with a GINF of 36.1 +/- 2.2 mumol.kg-1.min-1 (6.5 +/- 0.4 mg.kg-1.min-1), and obesity caused an increase in IR in NIDDM, with a GINF of 21.1 +/- 1.4 mumol.kg-1.min-1 (3.8 +/- 0.25 mg.kg-1.min-1) in the obese NIDDM subjects. Therefore, approximately 61% of the IR in obese NIDDM subjects is due to NIDDM, with 39% due to obesity, demonstrating a greater impact of NIDDM than of obesity in causing IR. The correlation between GINF and BMI was much better in normal subjects (r = -0.75) than in NIDDM subjects (r = -0.50) as was the relationship between fasting insulin level and BMI (r = -0.59 in normal subjects, r = -0.48 in NIDDM subjects). As expected, the fasting insulin level was also strongly correlated to GINF in normal subjects (r = -0.61); however, this relationship was weaker in NIDDM subjects ( r = -0.46). In conclusion, 1) obesity has a major impact to cause insulin resistance in nondiabetic subjects, but the effect of obesity on IR in NIDDM is less; 2) NIDDM per se is the major contributor to IR in NIDDM; and 3) the fasting insulin level is a better surrogate marker of IR in nondiabetic subjects than in NIDDM patients.

Adult↗
PubMed1994

Worsening right flank pain over a 24-hr period.

AML is a benign renal tumor composed of variable quantities of mature vascular, smooth muscle and fatty elements. They occur as an isolated finding, classically in middle-aged females, or in association with tuberous sclerosis. When symptomatic, they typically present with flank pain secondary to hemorrhage. CT is the diagnostic imaging modality of choice. The diagnosis can usually be made based on the recognition of fat within the lesion. When discovered, asymptomatic lesions are generally monitored by follow-up imaging studies, and if they remain stable, no intervention is required. Arterial embolization has become the recommended treatment of choice in some instances, particularly in cases with associated hemorrhage.

Adult↗
PubMed1994

The value of duplex sonography after peripheral artery angioplasty in predicting subacute restenosis.

OBJECTIVE: The purpose of this study was to determine if abnormal findings on duplex sonographic examination after peripheral artery angioplasty correlate with the subsequent recurrence of a stenosis. SUBJECTS AND METHODS: We used duplex sonography to examine 35 stenoses in 23 patients within 48 hr after the patients had angioplasty to treat these stenoses. Patients were followed up for 3 years by using one or more of the following: assessment of signs and symptoms, monitoring of peripheral pulses, pulse volume recordings, and angiography. Life tables were constructed to compare long-term patency with the presence of abnormal findings seen on duplex sonograms. Abnormal findings at the dilated segment included a blood-flow velocity greater than 120 cm/sec or a residual elevated velocity ratio greater than 1.4 or 2.0 immediately after angioplasty. RESULTS: Twelve (34%) of 35 angioplasty sites showed recurrent stenosis before 36 months. Patency at 24 months was calculated for velocities less than 120 cm/sec vs velocities of 120 cm/sec or greater (41% vs 68%), for velocity ratios less than 1.4 vs ratios of 1.4 or greater (63% vs 57%), and for velocity ratios less than 2.0 vs ratios of 2.0 or greater (54% vs 74%). We found no significant difference in patency between those patients with normal findings and those with abnormal findings on duplex sonographic examination after angioplasty. CONCLUSION: Abnormal findings on duplex sonograms obtained immediately after peripheral angioplasty cannot be used to predict subacute restenosis.

Angioplasty, Balloon↗
PubMed1992

Peripheral arterial Doppler ultrasonography: diagnostic criteria.

Fifty-one patients (86 legs) were studied from the aorta to the popliteal artery with both duplex ultrasonography and arteriography with the intention of establishing diagnostic ultrasonographic criteria for degrees of stenosis greater than 50% and determining the effect of multi-segment disease on the accuracy of these criteria. Receiver operator characteristic curves were used to determine diagnostic criteria for greater than 50%, greater than 70%, greater than 90% diameter stenoses or occlusions. A stenosis of greater than 70% was diagnosed either if the peak systolic velocity was more than 160 cm/sec (sensitivity 77%, specificity 90%) of if there was an increase in peak systolic velocity of 100% with respect to the arterial segment above the stenosis (sensitivity 80%, specificity 93%). Sequential stenoses were detected with lesser sensitivities. Ratio criteria were more accurate than peak systolic velocity for all degrees of stenosis. For detection of occlusion, duplex ultrasonography was 92% sensitive and 99% specific.

Arterial Occlusive Diseases↗
PubMed1992

Acute limb ischemia.

Acute ischemia of the extremity may be due to arterial occlusion from spontaneous thrombosis, embolus, arterial bypass graft thrombosis, trauma, or spasm. The presence of occlusion or stenosis can be determined noninvasively with the use of duplex Doppler ultrasonography. Most patients will require arteriography prior to thrombolytic or surgical therapy. New techniques, such as percutaneous aspiration thrombolectomy, expand the role of radiologic percutaneous therapy of the acutely ischemic limb. Prompt diagnosis and therapy are required to avoid limb loss or systemic metabolic complications from reperfusion of a dying limb.

Angioplasty, Balloon↗
PubMed1991

Screening recommendations for gestational diabetes mellitus.

As a result of extensive experiences in multiple centers and a review of the current literature, we conclude that a plasma glucose level obtained 1 hour after a 50 gm oral glucose challenge is the "best" gestational diabetes mellitus screening test. This universal screening is performed at least once during pregnancy. The screening threshold should be no higher than 140 mg/dl, or an unacceptable loss in sensitivity occurs. Universal screening for gestational diabetes mellitus is justified by morbidity reduction, cost, and protocol simplicity and ease.

Blood Glucose↗
PubMed1990

Evaluation of the peripheral arteries with duplex US after angioplasty.

Duplex ultrasound (US) was performed in 22 patients before and immediately after percutaneous transluminal balloon angioplasty (PTA) for peripheral artery stenoses or occlusions. Two patients underwent PTA on two occasions, and one patient underwent PTA of each lower extremity, resulting in 25 duplex US imaging pairs at a total of 40 PTA sites. The criterion for significant stenosis on duplex US studies was an increase in peak systolic velocity of at least 100% compared with the velocity in the arterial segment proximal to the lesion (velocity ratio, greater than or equal to 2.0). For 22 paired duplex US studies, pulse volume recordings or ankle-brachial indexes were obtained before and after PTA. After PTA, eight patients had residual high velocity ratios at 12 PTA sites. Only two of these patients had a residual hemodynamic stenosis as determined with post-PTA arteriography, pulse volume recordings, or ankle-brachial indexes. In this study, duplex US that was performed immediately after PTA for evaluation of residual stenosis was frequently misleading.

Angiography↗