Pneumatic compression therapy using the EQ Press accelerates lymphatic flow in healthy equine forelimbs as determined by lymphoscintigraphy.

OBJECTIVE: Limb lymphedema in horses can be debilitating and painful. Pneumatic compression therapy has shown significant benefits for people suffering from lymphedema. The objective of this study was to determine the effect of a novel, equine-specific pneumatic compression device on the lymphatic flow of healthy horse forelimbs as determined by Tc-99m sulfur colloid lymphoscintigraphy. ANIMALS: 6 healthy Thoroughbreds. PROCEDURES: In a randomized crossover design, horses underwent bilateral forelimb lymphoscintigraphy following subcutaneous injection of Tc-99m sulfur colloid at the coronary band as untreated control or with pneumatic compression therapy using the EQ Press. Lateral, static images were obtained of the distal limb (time 0 to 60 minutes) and proximal limb (time 30 to 60 minutes) using a standard gamma camera. Lymphatic flow was determined by assigning a score to the time point at which Tc-99m sulfur colloid was first visualized at the level of the accessory carpal bone (1 to 7) in the distal limb and the cubital lymph node (1 to 4) in the proximal limb. RESULTS: EQ Press treatment led to a significantly faster lymphatic flow of Tc-99m sulfur colloid to the predetermined anatomic locations of the accessory carpal bone (P = .002) in the distal limb and the cubital lymph node (P = .001) in the proximal limb. CLINICAL RELEVANCE: Pneumatic compression therapy as provided by an equine-specific device encouraged lymphatic flow in healthy, nonedematous equine forelimbs. These data support further study of the EQ Press for pneumatic compression therapy in horses clinically affected by lymphedema and lymphatic drainage disorders.

Utilization of Indocyanine Green to Aid in Identifying Sentinel Lymph Nodes in Merkel Cell Cancer.

BACKGROUND: Merkel cell carcinoma (MCC) is a relatively rare skin cancer with high rates of regional lymph node involvement and metastatic spread. National Comprehensive Cancer Network guidelines recommend sentinel lymph node biopsy (SLNB) for staging purposes. The goal of this study is to report our experience utilizing indocyanine green (ICG) fluorescence-based technology to aid in SLNB detection in MCC. METHODS: Consecutive MCC patients who underwent SLNB with radioisotope lymphoscintigraphy, with intraoperative handheld gamma probe, and ICG-based fluorescence imaging from 2012 to 2017 were prospectively studied (Cohort A). A group of historical controls that underwent SLNB for MCC with radioisotope lymphoscintigraphy and vital blue dye (VBD) (lymphazurin or methylene blue dye) was also analyzed (Cohort B). RESULTS: Twenty-four consecutive patients underwent SLNB with lymphoscintigraphy and ICG-based fluorescence and 11 controls underwent SLNB with lymphoscintigraphy and VBD. The localization rate by node with VBD was 63.6% and ICG-based fluorescence was 94.8%. For two patients, a positive sentinel lymph node (SLN) was detected only by ICG-based fluorescence and the nodes were not detected by gamma probe and one patient's only positive node was identified via ICG fluorescence only. VBD or gamma probe did not identify any unique positive SLNs in either cohort B or either cohort, respectively. CONCLUSIONS: In this study, we indicate that ICG-based fluorescence is not only feasible to augment SLN identification, but it has a higher node localization rate as compared to blue dye and it was able to identify positive SLNs otherwise missed by gamma probe. This study suggests the importance of utilizing two modalities to augment SLN identification and that ICG-based fluorescence may be able to identify nodes that would have been otherwise missed by gamma probe. We will continue to follow these patients and enroll more patients in this prospective study to further determine the role that ICG-based fluorescence has in identifying sentinel lymph nodes in MCC.

Delayed small bowel transit in children with cystic fibrosis and pancreatic insufficiency.

OBJECTIVE: Gastrointestinal disturbances are common in people with cystic fibrosis (CF); however, motility studies in this population have yielded inconsistent results. This study examined gastric emptying (GE) and small bowel transit (SBT) time in children with CF and pancreatic insufficiency compared with a healthy adult reference group. METHODS: Participants consumed an 8-ounce liquid test meal (approximately 550 calories, 32 g of fat) labeled with 300 µCi 99m technetium (Tc) sulfur colloid. Subjects with CF received a standard dose of pancreatic enzymes before consuming the test meal. GE and SBT were measured using a standard nuclear medicine scan. GE was determined after correcting for 99mTc decay in both anterior and posterior images. SBT was determined by following the movement of the tracer from the stomach to the cecum. The percentage arrival of total small bowel activity at the terminal ileum and cecum/ascending colon at 6 hours was used as an index of SBT. A 1-way analysis of covariance was performed for comparisons between groups after adjustment for age, sex, and body mass index. RESULTS: Subjects with CF (n = 16) had similar GE compared with the healthy reference group (n = 12); however, subjects with CF had significantly prolonged SBT time. At 6 hours, 37.2% ± 25.4% (95% CI 23.7-50.7) of the tracer reached the terminal ileum and colon compared with 68.6% ± 13.1% (95% CI 60.2-76.9) for the reference group (P < 0.001). After controlling for sex, age, and body mass index, this difference remained statistically significant (F = 12.06, adjusted R = 0.44, P < 0.002). CONCLUSIONS: Children with CF and pancreatic insufficiency had unaltered GE but delayed SBT time when taking pancreatic enzymes.

Quantitative imaging and sigmoidoscopy to assess distribution of rectal microbicide surrogates.

Understanding the distribution of microbicide and human immunodeficiency virus (HIV) within the gastrointestinal tract is critical to development of rectal HIV microbicides. A hydroxyethylcellulose-based microbicide surrogate or viscosity-matched semen surrogate, labeled with gadolinium-DTPA (diethylene triamine pentaacetic acid) and 99mTechnetium-sulfur colloid, was administered to three subjects under varying experimental conditions to evaluate effects of enema, coital simulation, and microbicide or semen simulant over 5 h duration. Quantitative assessment used single photon emission computed tomography (SPECT)/computed tomography (CT) and magnetic resonance imaging (MRI) imaging, and sigmoidoscopic sampling. Over 4 h, radiolabel migrated cephalad in all studies by a median (interquartile range) of 50% (29-102%; P<0.001), as far as the splenic flexure (approximately 60 cm) in 12% of studies. There was a correlation in concentration profile between endoscopic sampling and SPECT assessments. HIV-sized particles migrate retrograde, 60 cm in some studies, 4 h after simulated ejaculation in our model. SPECT/CT, MRI, and endoscopy can be used quantitatively to facilitate rational development of microbicides for rectal use.

Effect of massage technique on sentinel lymph node mapping for cancer of the breast.

Sentinel lymph node (SLN) mapping has substantially changed the nature of surgery for cancer of the breast. Variables such as tracer type, volume, injection site, timing, and surgical experience have all been extensively evaluated. However, little attention has been paid to the technique of massage for SLN procedures. We sought to evaluate the effects of three different massage techniques on mapping success or accuracy of SLN mapping for breast cancer. All lymphatic mapping procedures for breast cancer at our tertiary-care center were performed by three experienced surgeons using both colloid and dye followed by a 5-minute massage. All data pertaining to SLN identification, histopathology, tumor characteristics, and patient demographics were entered into the Breast Care Center database. Consistent and uniquely differing massage techniques classified as resuscitative, buffer, or knead-like were each used by a specific surgeon. The last 25 consecutive cases performed by two surgeons and the last 24 by one surgeon were evaluated. The overall rate of SLN identification was 97 per cent, and the overall accuracy was 98.7 per cent. There was no statistically significant difference in the rate of SLN identification or accuracy between techniques. The proportions of blue-stained SLNs were similar, but the resuscitative technique yielded fewer hot SLNs (Fisher's exact test, P = 0.02). This method also yielded one false negative case. The three different massage techniques yielded a similar number of blue-stained SLNs. The resuscitative technique yielded fewer hot SLNs than the kneading and buffer methods. Our results failed to demonstrate a superior breast massage technique for identifying sentinel nodes. A larger randomized trial is needed to confirm these findings.

[Value of 99mTc-Sulphur colloid scintigraphy in the diagnosis of intermittent digestive bleeding secondary to a case of jejunal angiodysplasia]. / Valor de la gammagrafía 99mTc-sulfuro coloidal en el diagnóstico de hemorragia digestiva intermitente secundaria a un caso de angiodisplasia en yeyuno.

We present the case of a 74 year old female patient, with clinical criteria of liver cirrhosis caused by hepatic C virus who required several admissions in our hospital over a five month period. She was given several blood transfusions because of repeated clinical manifestation of gastrointestinal bleeding without a clear origin. Her last admission was due to intermittent melenas, secondary anemia and hemodynamic angina. The patient's study included clinical analysis, fibrogastroscopy, colonoscopy, opaque enema, spiral CT and supraortic vessels arteriography. Because all the results to diagnose and locate the patient's disease were negative, she was referred to our service for a scintigraphy study. As it was an emergency case because of the patient's serious hemodynamic condition, a 99mTc-sulphur colloid scintigraphy was chosen, the results of which showed and located active gastrointestinal bleeding requiring urgent surgical intervention. The laparotomy with intrasurgical enterotomy and fibrogastroscopy undertaken ratified gastrointestinal bleeding, and the result of the biopsy of the jejunum removed in the intervention confirmed bowel angiodysplasia. Given the low incidence of gastrointestinal bleeding secondary to bowel angiodysplasia and absence of bibliographic references regarding the diagnosis of this disease in the above mentioned site by means of 99mTc-sulphur colloid scintigraphy in particular, we consider it interesting to highlight this case, in which the capability of this nuclear medicine technique for quick and non-invasive detection and location of gastrointestinal bleeding has been highly proven.

Valor de la gammagrafía 99mTc-sulfuro coloidal en el diagnóstico de hemorragia digestiva intermitente secundaria a una caso de angiodisplasia en yeyuno / Value of 99mTc-sulphur colloid scintigraphy in the diagnosis of intermittent digestive bleeding secondary to a case of jejunal angiodysplasia

Presentamos el caso de una paciente mujer de 74 años de edad, con criterios clínicos de cirrosis hepática por virus hepatitis C, que requirió varios ingresos hospitalarios en nuestro centro durante un período de cinco meses siendo politransfundida por presentar repetidos cuadros de sangrado intestinal de localización incierta. El último ingreso fue motivado por melenas intermitentes, anemia y angor hemodinámico secundario. El estudio de la paciente incluyó la práctica de analíticas, fibrogastroscopias, colonoscopias, enema opaco, angioTAC y arteriografía de troncos aórticos. Todas estas exploraciones fueron negativas para el diagnóstico y localización de la patología que presentaba la paciente, lo que motivó la solicitud a nuestro servicio de un estudio gammagráfico. Debido a la urgencia del cuadro por el severo estado hemodinámico de la paciente, se optó por la realización de una gammagrafía con sulfuro coloidal marcado con 99mTc donde se objetivó y se localizó la existencia de un sangrado intestinal activo efectuándose posteriormente una intervención quirúrgica de urgencia.La laparotomía con enterotomía y fibrogastroscopia intraoperatoria realizadas ratificaron la existencia de sangrado intestinal y el resultado de la biopsia de las asas yeyunales resecadas en la intervención fue compatible con el diagnóstico de angiodisplasia intestinal. Dada la baja incidencia de sangrado digestivo secundario a angiodisplasia de intestino delgado y la ausencia de referencias bibliográficas relativas al diagnóstico de esta patología en dicha localización mediante la gammagrafía con sulfuro coloidal-99mTc en particular, consideramos interesante destacar este caso donde se demuestra la capacidad de este tipo de prueba en la detección y localización no invasiva y rápida del sangrado intestinal (AU)

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Can preoperative lymphoscintigraphy be used as a guide in treatment planning of breast cancer?

PURPOSE: The purpose of this study was to map the lymphatic drainage patterns of breast cancer with lymphoscintigraphy to evaluate the variability of drainage and to determine whether lymphatic mapping can help to increase the certainty of breast cancer staging. MATERIALS AND METHODS: Fifty women with breast cancer (mean age, 49 years) were included in the study. Lymphoscintigraphy was performed with 1 mCi Tc-99m rhenium sulfide colloid in a 2-ml volume injected into the four quadrants of the peritumoral area using a 25-gauge needle. Ten-minute dynamic images and 2-hour delayed static images were obtained in the anterior and lateral positions using a gamma camera with a high-resolution collimator. All patients had a modified radical mastectomy and axillary dissection. The results were evaluated with histopathologic findings of the axilla. RESULTS: Six patients had excision biopsies before surgery. Of 13 patients with centrally located tumors, 84% had axillary lymphatic drainage, whereas 53% drained to internal mammary lymphatics. Of 23 patients with outer quadrant tumors, 4 showed no lymphatic drainage and all of them had metastatic tumor in the axillary lymph nodes. Axillary drainage was seen in 82% of patients and internal mammary lymphatic drainage in 23%. Of eight patients with inner quadrant tumors, one patient with no lymphatic drainage was found to have metastases in the axilla. In this group, 62% had axillary and 50% had internal mammary lymphatic drainage, and one patient had supraclavicular drainage. CONCLUSIONS: Lymphoscintigraphy indicates that drainage routes may vary, and thus it may play a guiding role in patients with breast cancer who need radiotherapy. In patients with internal mammary lymphatic drainage, the accuracy of radiotherapy planning may increase if internal mammary lymphoscintigraphy is added to the protocol. In patients with internal mammary drainage, obtaining an internal mammary lymphatic biopsy during surgery will also increase the accuracy of staging.

The effects of postinjection massage on the sensitivity of lymphatic mapping in breast cancer.

BACKGROUND: The technique of lymphatic mapping and sentinel lymph node (SLN) biopsy is rapidly becoming the preferred method of staging the axilla of the breast cancer patient. This report describes the impact of postinjection massage on the sensitivity of this surgical technique. STUDY DESIGN: Lymphatic mapping at the H Lee Moffitt Cancer Center is performed using a combination of isosulfan blue dye and Tc99m labeled sulfur colloid. Data describing the rate of SLN identification and the node characteristics from 594 consecutive patients were calculated. Patients who received a 5-minute massage after injection of blue dye and radiocolloid were compared with a control group in which the patients did not receive a postinjection massage. RESULTS: When compared with controls, the proportion of patients who had their SLN identified using blue dye after massage increased from 73.0% to 88.3%, and the proportion of patients who had their SLN identified using radiocolloid after massage increased from 81.7% to 91.3%. The overall rate of SLN identification increased from 93.5% to 97.8%. The proportion of nodes that were stained blue among those removed increased from 73.4% to 79.7% after massage. CONCLUSIONS: As experience increases with this new procedure, the surgical technique of lymphatic mapping continues to evolve. The addition of a postinjection massage significantly improves the uptake of blue dye by SLNs and may also aid in the accumulation of radioactivity in the SLNs, further increasing the sensitivity of this procedure.

Propagation of viral-size particles in lymph and blood after subcutaneous inoculation.

OBJECTIVE: We investigated the propagation of viral-size particles by lymph and blood after subcutaneous injection. METHODS: In the canine model, transport of [99mTc] sulfur colloid particles of different sizes was studied in different settings in venous blood and lymph for 45 minutes after inoculation. RESULTS: The mean arrival time of particles in the blood was 2.10+/-0.46 minutes and 8.87+/-1.72 minutes in the lymph. Lymph flow in the canine leg was 28.79 +/-2.09) microl/min and was increased by leg massage. The particle concentration was 1000 times higher in the lymph fluid than in blood. Particle flux values were comparable in blood and lymph. The accumulation of particles in blood initially rose faster than in lymph. Accumulation in lymph rises slower but continues longer and reaches higher values. Ninety percent of the inoculum remains at the injection site for at least 45 minutes. Particle size matters more in blood distribution. Leg massage enhances particle transport by lymph. CONCLUSIONS: After subcutaneous injection, viral-size particles initially arrive in the blood and later in the lymph. Accumulation in lymph and blood increases for a prolonged time after inoculation. Results suggest possibilities for limiting the spread of infectious matter by early local antiviral treatment.

Acute effect of nicotine patch on gastric emptying of liquid and solid contents in healthy subjects.

The effect of nicotine on gastric emptying remains controversial. Gastric emptying is delayed in chronic smokers after smoking high-dose nicotine cigarettes, but it is unchanged after chewing nicotine gums. No information is available on the effect of transdermal nicotine patches on the gastric emptying of solid and liquid contents in healthy nonsmokers. Our objective was to prospectively evaluate the effect of the nicotine patch on gastric emptying of liquid and solid contents in healthy nonsmokers. Ten healthy nonsmoking volunteers underwent a baseline dual-isotope gastric scintigraphy with [111In]-diethylenetriaminepantaacetic acid (DTPA) and [99mTc]sulfur colloid isotopes to evaluate prospectively the gastric emptying of liquid and solid contents, respectively. The gastric scintigraphy was repeated after placing a transdermal nicotine patch (Habitrol) for 12 hr designed to deliver 14 mg of nicotine per day. Plasma nicotine level was measured prior to baseline gastric scintigraphy and after 12 hr placing the nicotine patch. Plasma nicotine was absent in all subjects at baseline and but was significantly elevated after 12 hr of nicotine patch (P < 0.009). The mean half-emptying times (T1/2) for the gastric emptying of liquids before and after nicotine patch placement were 31.2+/-23.3 and 25.6+/-8.4 min, respectively (P = 0.498). The mean T1/2s for the gastric emptying of solids before and after nicotine patch placement were 70.1+/-34.0 and 59.7+/-31.4 min, respectively (P = 0.202). There was no correlation between the plasma nicotine level and gastric emptying of liquid and solid contents (correlation coefficient = -0.23 and -0.01, respectively). In conclusion, acute transdermal delivery of nicotine does not affect the gastric emptying of solid and liquid contents in healthy nonsmoking subjects.

Scintigraphic imaging and absorption of a 5-aminosalicylic acid enema in patients with ileorectal anastomosis.

UNLABELLED: Ileorectal anastomosis (IRA) is a possible surgical treatment for hyperacute and drug-unresponsive forms of ulcerative colitis (UC). UC relapses in the rectal remnant usually are prevented by chronic administration of 5-aminosalicylic acid (5-ASA) in topical formulations. The relationships between intestinal absorption and pattern of luminal spread of 5-ASA enemas are still unknown in patients with IRA. We correlated the absorption of a 5-ASA enema with its spread in the distal bowel of patients with IRA as assessed by 99mTc radioenema imaging. METHODS: Eight patients with UC in remission and previous IRA received a therapeutic 50-mL 5-ASA enema labeled with 99mTc-sulfer colloid. Absorbed 5-ASA and its major metabolite, acetyl 5-ASA, were measured in plasma, and dynamic images of radiolabeled enema were obtained for 6 h. The retrograde ileal spread (RIS) was determined and expressed as percentage of total enema radioactivity. Plasma levels of 5-ASA and acetyl 5-ASA were measured in six healthy volunteers after administration of the same enema volume with no radiolabeling. RESULTS: The mean 5-ASA plasma level was 0.70 microg/mL (range 0.37-0.95 microg/mL) in patients and 0.96 microg/mL (range 0.78-1.16 microg/mL) in healthy volunteers (P = not significant), and the mean acetyl 5-ASA plasma levels were 0.89 microg/mL (range 0.44-1.19 microg/mL) and 0.84 microg/mL (range 0.51-1.02 microg/mL), respectively (P = not significant). Radioenema imaging allows RIS assessment of patients with IRA. The mean value was 8.5% (range 2%-19.3%) of administered radioactivity, which correlated significantly with the total absorption of 5-ASA in the IRA group (P = 0.033, linear correlation test). Rectal wall contractions recognized by dynamic radioenema imaging were defined as a common cause of RIS episodes. CONCLUSION: In IRA patients, 5-ASA plasma levels were similar to those in healthy volunteers after administration in enema. Only part of a 50-mL 5-ASA enema reaches the ileum, and radiolabeled imaging shows the degree and number of these RIS episodes. The absorption of 5-ASA can increase in patients compared with healthy volunteers, in the presence of either occasional but significant ileal spread associated with postural factors and abdominal wall contraction or multiple moderate episodes of radioenema backdiffusion related to rectal wall motility.

Improved nutrition after the detection and treatment of occult gastroparesis in nondiabetic dialysis patients.

Malnutrition in dialysis patients is of multifactorial etiology and is associated with greatly increased morbidity and mortality. A low serum albumin level is one of the most powerful predictors of death and may persist despite optimization of the dialysis prescription. We retrospectively reviewed our experience in improving nutrition in nondiabetic patients with unexplained hypoalbuminemia. Using radionuclide solid-phase gastric emptying scans, we identified 6 patients who had occult gastroparesis. These patients (one on hemodialysis and five on peritoneal dialysis) were then treated with prokinetic medications (erythromycin elixir or metoclopramide) selected on the basis of their effectiveness in improving the scanning results after being given intravenously. Gastric emptying half-times improved from a median of 122 minutes (range, 95 to >300 minutes; normal, < or = 90 minutes) to 12 +/- 2 minutes (mean +/- SEM). The serum albumin increased from 3.3 +/- 0.04 g/dL to 3.7 +/- 0.08 g/dL at 3 months, with every patient's value higher than 3.5 g/dL. This improvement was statistically significant (P = 0.008) over the 5-month period of observation, which encompassed the 2 months before and 3 months after treatment. There was a linear improvement (P = 0.008) that showed a quadratic trend (P = 0.078) for a plateau at the final sampling point. The serum blood urea nitrogen, creatinine, and hematocrit levels remained unchanged (P > 0.1). We conclude that gastric emptying scans are valuable in identifying occult gastroparesis in high-risk patients and can guide the selection of prokinetic therapy, which may significantly increase serum albumin levels.

Sentinel lymph node biopsy, an alternative to elective axillary dissection for breast cancer.

BACKGROUND: Axillary metastases remain an important prognostic indicator in breast cancer. Axillary lymphadenectomy (ALND) carries significant morbidity and is unnecessary in most patients with early breast cancer; thus, sentinel lymph node (SLN) biopsy has been advocated for axillary staging. We studied the SLN identification rate and its accuracy in predicting axillary metastases. METHODS: One hundred nineteen women with breast carcinoma underwent SLN and ALND. Lymphoscintigraphy was performed using Technetium99 sulfur colloid supplemented by Isosulfan blue dye. Hematoxylin/eosin-stained lymph node sections were examined by light microscopy. RESULTS: The SLN identification rate was 81%. One SLN was negative (1%) in a patient with axillary disease. SLN histology correctly predicted the absence of axillary disease in 98.6%. Sensitivity, specificity, and positive and negative predictive values were 96%, 100%, 100%, and 99%, respectively. CONCLUSIONS: Sentinel lymph node biopsy accurately predicts total axillary status and is valuable in the surgical staging of breast cancer.

Retrograde colonic spread of a new mesalazine rectal enema in patients with distal ulcerative colitis.

BACKGROUND: Rectal treatment with mesalazine enemas is the first-line therapy for distal ulcerative colitis. In order to improve the benefits of rectal therapy, a new 60 mL 5-ASA rectal gel enema preparation has been developed using a device which excludes direct contact of the inert propellant gas with the active drug. The purpose of the present study was to assess by scintigraphy the colonic distribution of this new mesalazine rectal gel enema. METHODS: Twelve patients with active ulcerative colitis were administered 4 g of the mesalazine rectal enema labelled with 100 MBq technetium sulphur colloid (99mTc-SC). Anterior scans of the abdomen were acquired at intervals for 4 h. Scans were analysed to evaluate the extent of retrograde flow and homogeneity of distribution of the radiolabelled enema in the rectum, sigmoid, descending and transverse colon. In addition, plasma levels of 5-ASA and Ac-5-ASA were measured for 6 h. RESULTS: All patients retained the entire rectal gel throughout the course of the study without reporting adverse events. In 11 out of 12 patients (92%) the gel had spread homogeneously beyond the sigmoid colon and had reached the upper limit of disease in all cases. The maximum spread (splenic flexure) was observed in 6 out of 12 patients (50%) within the first 2 h. The systemic absorption of mesalazine and its metabolite Ac-5-ASA was low. CONCLUSIONS: The new mesalazine enema represents an adequate alternative and a further technological improvement in the topical treatment of distal ulcerative colitis.

Colonic spread of three rectally administered mesalazine (Pentasa) dosage forms in healthy volunteers as assessed by gamma scintigraphy.

BACKGROUND: Rectal administration of enemas, foams and suppositories is the most efficient method of delivering locally-acting drugs to the distal colon, sigmoid colon and rectum. Healthy volunteers provide an effective population to compare different formulations for rectal drug delivery. However, there is still only limited comparative information available on the dispersion of such dosage forms in human subjects. Therefore, the objective of this scintigraphic study was to compare colonic spread of an enema, a rectal foam and a suppository formulation in healthy volunteers. METHODS: This was a randomized, crossover study in eight healthy male volunteers. Each received Pentasa rectal formulations as either a 100 mL suspension enema (1 g mesalazine), one actuation of a non-CFC propellant rectal foam (1 g mesalazine in 5 mL concentrate, expanding to 40 mL on actuation), or one suppository (1 g mesalazine) on three separate occasions. The spread of the radiolabelled formulations was assessed over a 4-h period by gamma scintigraphy. RESULTS: The formulations were retained by all subjects for the whole of the 4-h imaging period. The enema spread to the splenic flexure in 7 out of 8 subjects, but was retained in the rectum and sigmoid colon in one individual. The foam spread as far as the descending colon in four subjects. In the remaining individuals the foam was retained in the rectum and sigmoid colon. The spread of the suppository was limited and confined to the rectum. CONCLUSIONS: The findings of this study are consistent with previous research and support the intended clinical uses of the enema, foam and suppository formulations to treat distal ulcerative colitis, proctosigmoiditis and proctitis, respectively. The results highlight the potential of gamma scintigraphy in providing in vivo 'proof of concept' data to help verify the targeting of pharmaceutical products to their intended site of delivery.

Distribution of mesalazine enemas in active and quiescent ulcerative colitis.

BACKGROUND: The efficacy of mesalazine enemas depends on intraluminal concentration of the drug and is therefore limited by the enema distribution in the colon. Active ulcerative colitis changes colon motility and this leads to uncertainty about enema spread. AIM: To assess the influence of disease activity on enema distribution, we conducted a physician-blinded, longitudinal study of the retrograde spread of three mesalazine enemas. METHODS: Thirty-one patients with mild to moderate ulcerative colitis were subdivided into three groups, and treated with 2 g mesalazine in 30 mL (group I, n = 10), 4 g mesalazine in 60 mL (group II, n = 12) or 1 g mesalazine in 100 mL (group III, n = 9). All patients received oral mesalazine 500 mg t.d.s. Enemas were labelled by adding 10 MBq (99mTc)technetium-sulphur colloid. Anterior scintigraphic images were taken at the start of the study and after 12 weeks of therapy; retrograde spread was assessed by calculating the percentage of the enema in each colonic segment. RESULTS: The activity score of ulcerative colitis diminished significantly after 12 weeks of treatment, but five patients dropped out of the study. At the start of treatment enema activity in group I was mainly concentrated in the sigmoid (99%); in group II activity was found in the rectum (9%), the sigmoid (61%) and the descending colon (15%); in group III activity was distributed between the sigmoid (66%) and descending colon (25%). The colonic distribution of mesalazine enemas was not influenced by disease activity. CONCLUSION: Volume, but not disease activity, is the important determinant of retrograde colonic spread of mesalazine enemas in ulcerative colitis.

Selective radionuclide localisation in primary liver tumours (pilot study).

The therapeutic potential of 131I-Lipiodol was investigated in 8 patients with cholangiocarcinoma (CCA) and 15 patients with hepatocellular carcinoma (HCC). Patients received one or two doses of 131I-Lipiodol via hepatic arterial injection. The mean total administered activity was 668 (SD 325) MBq in CCA and 953 (SD 477) MBq in HCC. One patient with CCA retained 131I-Lipiodol. The cumulative radiation dose was 9.6 Gy to tumour, 6.4 Gy to liver and 1.5 Gy to lung. The patient remained asymptomatic with no evidence of tumour 30 months from the start of treatment, whereas the remaining 7 patients exhibited tumour progression. The mean survival in CCA was 11.6 (SD 14.5) months. All 15 patients with HCC retained 131I with tumour: liver ratios of up to 30:1. The mean cumulative radiation dose was 34.7 (SD 32.4) Gy to tumour, 3.3 (SD 1.5) Gy to liver and 4.4 (SD 2.3) Gy to lung. The mean dose per administered activity was 3.8 (SD 4.1) cGy/MBq. Partial response (reduction in tumour size > 50%) was observed in 6 patients (40%). The mean survival was 7.1 (SD 6.0) months. 131I-Lipiodol can deliver highly selective internal irradiation to foci of HCC with evidence of objective response and may be the treatment of choice for patients with cirrhosis and a small tumour.

Evaluation of gastric emptying using radionuclides: gastric lavage versus ipecac-induced emesis.

STUDY OBJECTIVES: To compare the efficacy of gastric lavage and ipecac-induced emesis by using a radionuclide marker in a simulated overdose and to determine the amount of material recoverable after lavage fluid appears clear. DESIGN: Case-control, prospective cross-over study. SETTING: Nuclear medicine department of Valley Medical Center, Fresno, California. TYPE OF PARTICIPANTS: Fourteen male and five nonpregnant female adult volunteers with no pre-existing gastrointestinal disease and no medication use. INTERVENTIONS AND MEASUREMENTS: In phase 1, each volunteer ingested 30 capsules labeled with a measured amount of Tc99m with 75 mL H2O followed in five minutes by ipecac-induced emesis. In phase 2, two to four weeks later, each subject was lavaged after ingesting 30 labeled capsules. After lavage appeared clear, a 1,000-mL supplemental lavage was done and analyzed separately. All emesis or gastric lavage fluid was collected and measured for tracer activity. RESULTS: All subjects in the ipecac group vomited with an average time from ipecac to emesis of 19 minutes. Two subjects withdrew from the study, refusing to complete lavage due to discomfort. Based on retrieved material, ipecac-induced emesis returned significantly more tracer (mean +/- SD, 54.1 +/- 21.3%) than lavage until clear (mean +/- SD, 30.3 +/- 17.4%) (P = .0021). Supplemental lavage returned 12.9% of the total recovered marker (SD, 11.6%). The total of initial and supplemental returns from lavage was 35.5% (SD, 21.0%). This return was significantly less than that returned by ipecac-induced emesis (P = .016). CONCLUSION: In this study, ipecac-induced emesis was significantly more effective than gastric lavage in emptying the stomach after simulated overdose. Significant amounts of ingested material are recoverable in gastric lavage return after it appears clear.

Coronary thrombolysis. Comparative effects of intracoronary administration of recombinant tissue plasminogen activator and urokinase.

We employed a canine model of coronary thrombosis, induced by injection of radioactive blood clot, via a catheter placed in the left anterior descending coronary artery, to compare effects of intracoronary administration of recombinant tissue plasminogen activator (rtPA) and urokinase (UK) on rate and extent of coronary thrombolysis. Two doses of UK, 15,000 U/kg (UK15) and 30,000 U/kg (UK30) and two doses of rtPA, 0.25 mg/kg (rtPA.25) and 0.75 mg/kg (rtPA.75) were given. Drugs were infused over 45 min. Compared with the other regimens, rate and extent of coronary thrombolysis were significantly increased with rtPA.75. Also, despite a much higher dose of UK, coronary thrombolysis was similar with UK30 and rtPA.25. Compared with UK15, rate and extent of coronary thrombolysis were increased with rtPA.25. These results indicate that intracoronary administration of rtPA is superior to intracoronary UK in inducing thrombolysis.