Comparison of estrone and 17ß-estradiol levels in commercial goat and cow milk.

Increased levels of estrogen metabolites are believed to be associated with cancers of the reproductive system. One potential dietary source of these metabolites that is commonly consumed worldwide is milk. In North America, dairy cows are the most common source of milk; however, goats are the primary source of milk worldwide. In this study, the absolute concentrations of unconjugated and total (unconjugated plus conjugated) estrone (E(1)) and 17ß-estradiol (E(2)) were compared in a variety of commercial cow milks (regular and organic) and goat milk. A lower combined concentration of E(1) and E(2) was found in goat milk than in any of the cow milk products tested. The differences in E(1) and E(2) levels between regular and organic cow milks were not as significant as the differences between goat milk and any of the cow milk products. Goat milk represents a better dietary choice for individuals concerned with limiting their estrogen intake.

Gene expression monitoring for gene discovery in models of peripheral and central nervous system differentiation, regeneration, and trauma.

Gene expression monitoring using gene expression microarrays represents an extremely powerful technology for gene discovery in a variety of systems. We describe the results of seven experiments using Incyte GEM technology to compile a proprietary portfolio of data concerning differential gene expression in six different models of neuronal differentiation and regeneration, and recovery from injury or disease. Our first two experiments cataloged genes significantly up- or down-regulated during two phases of the retinoic acid-induced differentiation of the embryonal carcinoma line Ntera-2. To identify genes involved in neuronal regeneration we performed three GEM experiments, which included changes in gene expression in rat dorsal root ganglia during the healing of experimentally injured sciatic nerve, in regenerating neonatal opossum spinal cord, and during lipopolysaccharide stimulation of primary cultures of rat Schwann cells. Finally we have monitored genes involved in the recovery phase of the inflammatory disease of the rat spinal cord, experimental allergic encephalomyelitis, as well as those responsible for protection from oxidative stress in a glutamate-resistant rat hippocampal cell line. Analysis of the results of the approximately 70,000 data points collected is presented.

Mercaptoacetyltriglycine diuretic renography and output efficiency measurement in renal transplant patients.

Suspected urinary tract obstruction following renal transplantation presents a diagnostic dilemma. The purposes of this study were: (1) to establish a normal range of measurement of output efficiency (OE) in the renal transplant population, and (2) to assess prospectively the usefulness of OE in the setting of allograft obstruction. Twenty-two renal transplant patients with stable renal function and no evidence of hydronephrosis on serial ultrasound examination had a diuretic mercaptoacetyltriglycine scan with calculation of OE. Three renal transplant patients with confirmed graft obstruction were also studied. Standard qualitative and quantitative parameters as well as OE were calculated. The mean OE for the 22 normal renal transplant patients was 86.3%+/-3.7% (range: 77%-91%). OE values in the three obstructed patients were 59%, 68% and 75% respectively. It is concluded that OE should normally exceed 77% in renal graft recipients. OE is a promising means of diagnosing functional obstruction in these patients.

Acute renal failure in critically ill patients: evaluation of an ultrasound contrast agent.

The purpose of the present paper was to evaluate an ultrasound contrast agent (Levovist) in patients with oliguric acute renal failure (ARF) in order to assess renal vascularity, differentiate acute tubular from cortical necrosis and predict prognosis. Ten intensive care unit (ICU) patients with oliguric ARF were prospectively investigated by ultrasound including colour, power and pulsed Doppler before and after injection of Levovist. Doppler signals were graded as absent, equivocal or present from the inner and outer portions of the renal parenchyma, and these findings were correlated with clinical parameters and outcome. Only one patient had findings in keeping with acute cortical necrosis. All patients who survived had parenchymal vascularity while only three of six (50%) who died had parenchymal vascularity after Levovist. The ultrasound contrast caused no side effects and additional information was provided which improved diagnostic confidence, enabled appropriate classification of patients as having tubular or cortical necrosis and therefore added prognostic information.

Assessment of pediatric hydronephrosis using output efficiency.

UNLABELLED: Diagnosing obstruction in pediatric patients with hydronephrosis, and renal impairment is often difficult. Renal output efficiency (OE) is a parameter that may improve diagnostic accuracy by allowing normalization of washout according to renal function. The aims of this study were to define a normal range for OE in infants and children and to evaluate its diagnostic accuracy in cases with hydronephrosis. METHODS: Seventy-four children (91 hydronephrotic kidneys; median age, 4 mo; 22 girls and 52 boys) underwent 99mTc-labeled mercaptoacetyl-triglycine scintigraphy using intravenous volume expansion (15 ml/kg normal saline), furosemide diuresis and urethral catheterization, if vesicoureteric reflux was present. Images were interpreted by consensus of two or more experienced observers using visual assessment of the images, differential function and clearance half-time after furosemide (T(1/2)), as well as OE. The final diagnosis was based on surgical findings (n = 23 kidneys) or follow-up for >12 mo (n = 68). RESULTS: Final diagnosis in 22 of the 91 hydronephrotic kidneys was obstruction at the pelviureteric (n = 21) or vesicoureteric (n = 1) junction and no obstruction in the remaining 69. The overall diagnostic accuracy of OE was 89%. Using exhaustive search multivariate logistic regression analysis, only reduced OE (p < 0.001) and decreased renal uptake by visual assessment (p = 0.058) were independently predictive of obstruction (R2 = 0.726). In dilated but unobstructed kidneys, mean OE was 93% +/- 7.1%. In the normal kidneys, mean OE was 96% +/- 3.1%. CONCLUSION: OE improves the diagnostic accuracy of diuretic renography in children and neonates with hydronephrosis and suspected obstruction. Output efficiency should exceed 89% in normal kidneys and 79% in unobstructed, hydronephrotic kidneys.

Adenosine thallium-201 scans in patients undergoing elective non-cardiac surgery.

Dipyridamole Thallium-201 (201Tl) scintigraphy has been used widely for assessment of patients prior to vascular surgery. Recently, Adenosine has been reported to be a safe and useful alternative to Dipyridamole. The purposes of this study were to evaluate the safety and feasibility of the use of Adenosine, to evaluate the correlation of Adenosine 201Tl scans with coronary angiograms (when available) and to evaluate the effect of scan results on clinician management style. Fifty adults with abdominal aortic aneurysm or other vascular disease underwent an intravenous infusion of Adenosine in conjunction with initial and delayed planar 201Tl scans. Images were interpreted qualitatively and quantitatively by the consensus of two or more experienced observers with patients showing transient left ventricular dilatation or redistribution in one or more myocardial segments reported as being at high risk of peri-operative cardiac events. Of the 50 subjects studied, 49 tolerated the maximum infusion dose with 60% experiencing minor transient symptoms. Low (n = 30) and high risk (n = 20) patients were defined according to Adenosine 201Tl scans. Age, gender and clinical characteristics were similar in both groups. Thirteen (65%) high risk subjects had coronary angiography compared with only three (10%) low risk patients. Patients with high-risk 201Tl scans were also more likely to proceed to coronary revascularization prior to non-cardiac surgery [5/20 (25%) vs 1/30 (3%)]. The positive predictive value of high risk 201Tl scans for coronary artery disease was 85%. Thus, Adenosine is considered a useful and safe alternative to Dipyridamole.(ABSTRACT TRUNCATED AT 250 WORDS)

Twice-daily dosing of loracarbef 200 mg versus 400 mg in the treatment of patients with acute maxillary sinusitis.

Loracarbef is an oral synthetic beta-lactam antibiotic in the new carbacephem class. We conducted a multicenter, randomized, double-blind, parallel-group study to compare the efficacy and safety of loracarbef 200 mg twice daily (BID) and 400 mg BID when given orally for 10 days to patients 12 years of age and older with acute maxillary sinusitis. Because sinus aspirates for culture are not routinely obtained in the management of acute maxillary sinusitis, antimicrobial therapy usually is selected empirically. This study was designed to provide data simulating the usual clinical practice of treatment without sinus aspiration. Two hundred nine patients who met the entry criteria, which included abnormal pretherapy sinus radiographs compatible with acute maxillary sinusitis and symptoms of fewer than 4 weeks' duration, qualified for the clinical analyses. Of the 106 clinically qualified patients assigned to the 200-mg BID group, favorable clinical responses (cure and improvement) were noted in 86 (81.1%) patients. Of the 103 clinically qualified patients assigned to the 400-mg BID group, 84 (81.6%) patients had favorable clinical responses. These results compare favorably with accepted clinical response rates of 70% to 80% for beta-lactams selected on an empiric basis. At the end of the treatment period, favorable radiologic responses (resolved and improved) and favorable clinical responses occurred in 55 (51.9%) of the 106 clinically qualified patients in the 200-mg BID group and in 57 (55.3%) of the 103 clinically qualified patients in the 400-mg BID group. Mean roentgenogram scores for the clinically qualified patients were 2.3 for both groups before therapy and 1.3 and 1.5 after therapy for the 200-mg BID and 400-mg BID groups, respectively. The mean change from pretherapy to posttherapy by patient was 1.0 for the 200-mg BID group and 0.8 for the 400-mg BID group. There were no statistically significant differences between treatment groups in the incidence of specific adverse events reported during therapy. These data suggest that loracarbef 200 mg BID is comparable in efficacy and safety to loracarbef 400 mg BID in the treatment of patients with acute maxillary sinusitis.

How useful is ultrasonography in suspected acute osteomyelitis?

Sonographically detected subperiosteal fluid and periosteal irregularity have recently been proposed as diagnostic features of osteomyelitis. The purpose of this study was to determine the diagnostic accuracy of ultrasonography for suspected osteomyelitis. Nineteen patients were investigated prospectively with high-resolution ultrasonography for the presence of subperiosteal fluid or cortical irregularity. Diagnosis was established by surgery (three cases) or by results of other tests and clinical follow-up. Sixteen patients were diagnosed as having osteomyelitis, with positive ultrasonography in ten (sensitivity = 63%). Two ultrasonographic studies were false-positive; diagnostic accuracy was 58%. Thus, ultrasonographic results may be potentially misleading, emphasizing the importance of clinical judgment and results of other tests.

The role of high dose 67-gallium scintigraphy in staging untreated patients with lymphoma.

BACKGROUND: Gallium-67 (67Ga) scintigraphy has been reported to be of limited value in staging lymphoma patients. However, recent technical advances in radionuclide imaging have potentially enhanced the usefulness of this method. AIMS: The purposes of this study were to determine the current: (1) sensitivity and specificity and (2) impact on clinicians' treatment decisions of 67Ga scans performed at a teaching hospital. METHODS: There were 46 newly presenting patients with lymphoma (13 with Hodgkin's disease (HD) and 33 with non-Hodgkin's lymphoma [NHL]). Planar 67Ga scans were performed up to eight days following injection of 300 MBq (8 mCi) with images interpreted by consensus of two blinded observers; sensitivity and specificity were determined on a lesion by lesion basis in comparison to computed tomography (CT) scans, palpation of peripheral lymph nodes and abdominal lymphangiograms (n = 5). The contribution of 67Ga scans to clinicians' treatment decisions was also independently assessed by an experienced oncologist. RESULTS: Gallium-67 scan sensitivity and specificity were 80% and 96% for HD and 59% and 98% for NHL. Initial treatment plans were modified in three individuals (7%; 95% confidence intervals = 3-10%) due to lesions on the 67Ga scan not prospectively detected or considered equivocal on other tests. CONCLUSIONS: Only a small proportion of newly diagnosed lymphoma patients benefit from staging with state of the art planar high dose 67Ga imaging.

The significance of isolated gallium-67 uptake in the hilar lymph nodes of an untreated lymphoma patient.

A 69-year-old woman presented with non-Hodgkin's lymphoma of the right ilioinguinal region in whom bilateral uptake of Ga-67 in hilar lymph nodes was noted on thoracic SPECT. There were no Ga-67 abnormalities elsewhere within the thorax, and a chest CT scan was also normal. The patient received radiotherapy to the inguinal region and remained in clinical remission for 28 months following treatment. She subsequently relapsed at a number of peripheral lymph node sites, but not in the chest. The authors postulate that isolated hilar uptake of Ga-67 SPECT may not be clinically significant in some untreated patients with lymphoma. This scintigraphic finding should be interpreted cautiously, particularly when other chest imaging studies remain negative.

Effects of renal dysfunction on the pharmacokinetics of loracarbef.

Loracarbef, the first carbacephem antibiotic to undergo clinical development, is excreted primarily unchanged in the urine (> 90%). Data analyzed from subjects with various degrees of renal dysfunction who were given single oral doses of loracarbef indicated a linear relationship between creatinine clearance (CLCR) and plasma clearance [CLP (L/hr) = 0.106.CLCR (ml/min/1.73 m2)]. The mean area under the plasma concentration-time curve in normal subjects and in patients with severe renal insufficiency (no dialysis/receiving dialysis) was 32 micrograms.hr/ml and 1085 micrograms.hr/ml/103 micrograms.hr/ml, respectively. Therefore, for individuals with moderate renal insufficiency (CLCR, 10 to 49 ml/min/1.73 m2), the dose should be halved or the dosing interval doubled; patients with severe renal insufficiency who are not receiving dialysis should be treated with the normal dose given once every 3 to 5 days. Loracarbef is readily cleared from plasma by hemodialysis; dosing should be repeated after a hemodialysis treatment.

A case of metastatic malignancy masquerading as a hepatic hemangioma on labeled red blood cell scintigraphy.

A 36-yr-old woman with a past history of gastric neuro-endocrine carcinoma (carcinoid tumor) underwent 99mTc-red blood cell (RBC) scintigraphy for evaluation of a 2-cm echogenic liver mass demonstrated on ultrasound. Scan findings were typical of a cavernous hemangioma. On follow-up, however, there was progressive lesion enlargement; histopathology of the resected mass revealed neuro-endocrine carcinoma. This case report, one of the few examples of a false-positive 99mTc-RBC scan, highlights the need for cautious evaluation of focal liver masses, even when there are typical scintigraphic features of cavernous hemangioma.

Volume expanded diuretic renography in the postnatal assessment of suspected uretero-pelvic junction obstruction.

Controversy surrounds the role of 99mTc-diethylenetriamine pentaacetic acid renography in suspected uretero-pelvic junction obstruction in early life. Accordingly, we retrospectively reviewed 18 patients (28 hydronephrotic kidneys) with a mean age of 2 mo (range: 1 wk-6 mo) who underwent a total of 36 scans using intravenous volume expansion (10 ml/kg) and furosemide diuresis (1 mg/kg). Initial scans were classified as obstructed, not obstructed or indeterminate using differential renal function, furosemide washout T 1/2 and visual assessment of tracer clearance. Those initially classified as obstructed (n = 8) have been surgically confirmed. In the indeterminate (n = 6) and nonobstructed (n = 14) groups, three and two kidneys, respectively, developed obstruction on progress scans. Mean follow-up in the nonsurgical patients was approximately 9 mo (range: 4-17 mo). A total of 13 kidneys had developed obstruction by renographic criteria, and to date 12 have surgical confirmation. Our data indicate that: (1) scans classified as obstructed correlate well with surgery; (2) an initial classification of indeterminate or nonobstructed does not exclude later development of obstruction; and (3) serial scans correctly stratify children with possible uretero-pelvic junction obstruction.

Loracarbef (LY163892) versus amoxicillin/clavulanate in the treatment of acute purulent bacterial bronchitis.

In this single-blind study, 488 patients with acute bronchitis were randomly assigned to receive 400 mg of loracarbef twice daily or 500/125 mg of amoxicillin/clavulanate three times daily for seven days. Treatment efficacy was evaluated in 98 patients treated with loracarbef and in 99 treated with amoxicillin-clavulanate in whom pretreatment positive cultures of pathogens susceptible to both study drugs were found. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, and Klebsiella pneumoniae were isolated in pure or mixed cultures in 64% of the evaluable patients; S pneumoniae was found in 26%. Among the evaluable patients, the rate of favorable clinical responses (cure and improvement) in the loracarbef group (96 of 98 patients; 98.0%) was similar to that in the amoxicillin/clavulanate group (96 of 99 patients; 97.0%); the favorable bacteriologic response rates were also similar (93.7% vs 92.9%, respectively). Eight patients in the loracarbef group and nine in the amoxicillin/clavulanate group discontinued treatment because of adverse events. The events were presumed to be drug related in five of the loracarbef group and in seven of the amoxicillin/clavulanate group. During therapy, diarrhea was the most frequently reported event in both groups. However, it occurred in only 8.2% of the loracarbef-treated patients compared with 22.5% of the amoxicillin/clavulanate patients (P less than 0.001). It is concluded that both loracarbef and amoxicillin/clavulanate are safe and effective in the treatment of acute purulent bacterial bronchitis.

Loracarbef (LY163892) versus amoxicillin/clavulanate in the treatment of acute bacterial exacerbations of chronic bronchitis.

In this single-blind study, 579 patients with chronic bronchitis were randomly assigned to receive 400 mg of loracarbef twice daily or 500/125 mg of amoxicillin/clavulanate thrice daily for seven days. Treatment efficacy was evaluated in 129 of the loracarbef-treated patients and 120 amoxicillin/clavulanate-treated patients in whom pretreatment positive cultures of pathogens susceptible to both antibiotics were isolated. Three organisms predominated in either pure or mixed cultures in 57.0% of the evaluable patients: Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella (Branhamella) catarrhalis; H influenzae was isolated in 25.0% of the patients with single pathogens. Among the evaluable patients, favorable clinical responses (cure or improvement) were noted in 93.8% of the loracarbef-treated patients and in 95.0% of the amoxicillin/clavulanate-treated patients. A favorable bacteriologic response (pathogen eliminated or presumed eliminated) was found in 82.2% of loracarbef-treated patients and 90.0% of amoxicillin/clavulanate-treated patients. Six patients in the loracarbef group and 14 in the amoxicillin/clavulanate group discontinued treatment because of adverse events. The events were judged to be drug related in four loracarbef-treated patients and in 11 amoxicillin/clavulanate-treated patients. The incidence of diarrhea and other gastrointestinal symptoms was significantly more frequent in the amoxicillin/clavulanate group (13.5% and 5.6%) than in the loracarbef group (4.5% and 1.7%), while the incidence of severe headaches was significantly more frequent in the loracarbef than the amoxicillin/clavulanate group (7.2% vs 3.1%). It is concluded that loracarbef and amoxicillin/clavulanate are safe and effective in the treatment of acute bacterial exacerbations of chronic bronchitis.

Loracarbef (LY163892) versus cefaclor in the treatment of acute bacterial bronchitis.

In this double-blind study, 319 patients (133 men, 186 women) with acute bronchitis were randomly assigned to receive 200 mg of loracarbef twice daily (n = 160; mean age, 42 years) or 250 mg of cefaclor thrice daily (n = 159; mean age, 43 years) for seven days. Clinical and bacteriologic responses were assessed in 63 loracarbef-treated and 56 cefaclor-treated patients in whom pretreatment positive cultures of pathogens susceptible to loracarbef and cefaclor were found. Among these evaluable patients, a clinical cure was found in 68.3% of the loracarbef-treated patients and in 66.1% of the cefaclor-treated patients and improvement in 27.0% and 28.6%, respectively; the pathogen was eliminated in 7.9% and 10.7% and presumed eliminated in 82.5% and 82.1%, respectively. Three in the loracarbef group discontinued treatment because of adverse events, two of which (nausea, nausea/diarrhea/vomiting) were presumably related to the drug. Headache was reported by 9.4% of the 160 patients in the loracarbef group and 6.9% of the 159 patients in the cefaclor group; diarrhea by 5.6% and 6.9%, respectively; and dyspepsia/abdominal pain/gastrointestinal disorders by 5.6% and 4.4%, respectively. It is concluded that both loracarbef and cefaclor are safe and effective in the treatment of acute bacterial bronchitis.

Investigation of focal hepatic lesions: is tomographic red blood cell imaging useful?

Noninvasive diagnosis of cavernous hemangioma of the liver is an important step in the investigation of patients with focal hepatic lesions since biopsy may result in life-threatening hemorrhage. To determine the diagnostic accuracy of 99m-technetium red blood cell (99mTc-RBC) imaging with tomography, 50 patients with various types of focal liver lesions were studied. Thirty-two patients had 45 hemangiomas and 7 other benign lesions while 18 patients had either primary (n = 8) or secondary (n = 10) hepatic malignancies. Tomographic imaging identified 12 more hemangiomas than planar imaging, improving sensitivity from 53% to 80%, and was found most useful for detection of smaller lesions (mean size, 2.1 cm). Specificity for hemangiomas was 100% with all lesions greater than 1.9 cm showing the characteristic scintigraphic pattern of blood-pooling on delayed images. There was excellent agreement between 2 independent observers concerning interpretation of tomographic images (89% for the hemangioma group and 100% for other patients). Therefore 99mTc-RBC scintigraphy with tomography is an accurate diagnostic technique in the investigation of cavernous hemangiomas. Its major value resides in its ability to distinguish hemangiomas from other types of hepatic pathology.

Diagnosis and treatment of antenatal uropathies.

Thirty-five patients with significant fetal hydronephrosis detected on antenatal ultrasound had postnatal investigations which included ultrasound, 99mtechnetium diethylenetriamine pentacetic acid (99mTcDTPA) renal scans and micturating cystourethrograms. Antenatal and postnatal ultrasound were unable to determine reliably the level of obstruction causing the hydronephrosis. The 99mTcDTPA renal scan was useful in determining the necessity and timing of surgery, but could not exclude vesico-ureteric reflux. Seven patients required surgery in the neonatal period and a further seven children had surgery because of deterioration of the scan appearance on follow-up studies performed at 3, 6 and 12 months of age and then at longer time intervals. Twenty patients (almost 60%) have been managed conservatively for a mean of 28 months (range: 12 months-7 years) with no deterioration in renal function.