Lymphedema and lymphocysts following lymphadenectomy may be prevented by omentoplasty: A pilot study.

OBJECTIVES: Pelvic lymph node dissection as part of the staging surgery for cervical carcinoma interrupts the afferent lymphatics, so the lymph drains retroperitoneally. New surgical techniques designed to leave the peritoneum open after the retroperitoneal dissection, in particular the application of a pedicled omentoplasty along the dissection route, have been advocated to prevent the formation of lymphocysts and lymphedema. We investigated the possible benefit of pedicled omentoplasty in preventing lymphocysts and lymphedema following pelvic lymph node dissection. METHODS: In this pilot study with historical controls we compared the formation of lymphocysts and lymphedema following two different surgical techniques for pelvic node dissection: group I (historical controls), in which the dorsal peritoneum was left open, and group II, in which the dorsal peritoneum was left open with application of a pedicled omentoplasty. In these two groups of gynecologic patients, we compared the lymph flow patterns and the occurrence of lymphedema following systemic pelvic lymphadenectomy. The two groups were of comparable clinical status and consisted of 12 (group I) and 10 (group II) patients. Lymphocysts, if any, were detected by CT scan, the lymph flow patterns were visualized by dynamic lymphscintography, and lymphedema was visualized by physical examination and magnetic resonance imaging of the groin and the upper leg. RESULTS: In both groups a distinct intraperitoneal absorption of the lymph fluid was observed. Pedicled omentoplasty seemed to facilitate the absorption or transport of lymph fluid, resulting in less lymphedema in the upper leg. CONCLUSION: It appeared that leaving the dorsal peritoneum open to give the lymph stream the opportunity to pour into the abdominal cavity is important in preventing lymphocysts and lymphedema. The dynamic lymphscintigraphy described in this paper showed that the intraabdominal lymph flow is absorbed by the peritoneum and even more quickly by the pedicled omentum.

Tc-99m tetrofosmin myocardial distribution 4 hours post injection.

The recommended protocol for Tc99m tetrofosmin myocardial imaging suggests either a one- or two day imaging protocol so that stress and rest studies are sufficiently separated in time to allow optimum myocardium to background uptake ratios to differentiate between myocardial ischaemia and/or infarction. The biokinetic data for tetrofosmin suggest that no significant changes occur in myocardial distribution up to 180 minutes post injection. It is, therefore, necessary for two doses of the radiopharmaceutical and two separate studies to evaluate the myocardial status during stress and rest. This study assessed the differences between the 1 and 4 hour post injection SPET images obtained following peak exercise in 20 consecutively chosen patients. In addition, these images were compared to the rest images obtained on the following day after a second dose of the radiopharmaceutical was administered. In 4 patients, a one and four hour post injection study was also done during the rest phase. The results demonstrate significant changes in Tc-99m tetrofosmin distribution between the one hour and four hour post injection images. These differences are present during the stress as well as rest studies.

IL-6-induced anaemia in rats: possible pathogenetic implications for anemia observed in chronic inflammations.

Anaemia of chronic disease (ACD) is frequently found in rheumatoid arthritis (RA). In the pathogenesis of ACD both cytokines, such as tumour necrosis factor-alpha (TNF-alpha), IL-1 and IL-6 as well as a relative deficiency of erythropoietin (EPO), are thought to play a key role. In the present study the role of IL-6 in the pathogenesis of this anaemia was investigated. IL-6 was administered intraperitoneally to rats for 14 sequential days. It appeared that IL-6 was able to induce anaemia. No evidence for suppression of bone marrow erythropoiesis or enhanced sequestration of erythrocytes in the liver was found. However, decreased plasma and bone marrow iron contents were observed in anaemic rats. Blood loss in intestinal tissue was demonstrated using erythrocyte labelling with 99mtechnetium. Histologically this was associated with inflammatory cell infiltration, oedema and bleeding in the intestinal wall. In conclusion, IL-6 induced anaemia in rats. This anaemia was caused by intestinal blood loss.

Radiopharmaceuticals 1994. Nil desperandum. European Association of Nuclear Medicine Committees on Radiopharmaceuticals and Positron Emission Tomography.

On the basis of the discussions at a symposium held in Düsseldorf and attended by representatives of various interested bodies, European legislation as it affects radiopharmaceuticals is reviewed. Due consideration is given to the new, centralised and decentralised, registration procedures, effective since 1 January 1995. The dossier required to support an application for marketing authorisation is discussed, separate consideration being given to single-photon emitters, therapeutic radio-nuclides and positron-emitting radiopharmaceuticals. The role of the European Pharmacopoiea is also considered. It is concluded that the new, modified procedures for the registration of medicinal products in the European Union may actually inhibit free availability of radio-pharmaceuticals within the Community, and that there is a strong case for modification of the European Directives so that radiopharmaceuticals are placed in a separate category to therapeutic drugs, with less stringent registration requirements.

EEC directives and guidelines applicable to radiopharmaceuticals--1993. Status quo with particular emphasis on the registration of radiopharmaceuticals which were on the market prior to January 1992.

The manufacture, scale and supply of radiopharmaceuticals in the EEC is regulated by directives that are incorporated into the national laws of the member states. The situation as of 1 January 1993 was not too optimistic, however, as the processing of licensing applications had been completely misjudged. Not one product had been registered as of 1 January. The costs involved are also high and since the European market for radiopharmaceuticals is relatively small, the market cannot afford this. It would appear that the EEC directives are inadequate and too non-specific, so revision is indicated.

Criteria for the use of monoclonal antibodies, legislation and ethical considerations.

The criteria governing the in vivo use of monoclonal antibodies in humans are based upon a number of legal requirements with respect to radiation hygiene, pharmaceutical legislation, radiopharmaceutical legislation and regulations with respect to products arising from biotechnology. This in itself has led to a complicated situation which has undoubtedly restricted the development of valuable diagnostic and potential therapeutic agents. From the ethical point of view there are also important considerations, firstly with respect to the methods of producing antibodies, which has resulted in the discontinuation of the raising of antibodies in murine ascites, and secondly in consideration of the ethics of administering labelled antibodies to healthy volunteers and to patients who may not necessarily benefit personally from the procedure. These factors must be evaluated in the light of the EEC document 'Good clinical practice for trials in medicinal products in the European Community from the CPMP working party on Efficacy of Medicinal Products'.

Acute improvement of cardiac function with intravenous L-propionylcarnitine in humans.

As the myocardial carnitine content, a key control factor in myocardial oxidative metabolism and energy transfer, is reduced in heart failure, administration of L-propionylcarnitine (LPC), a potent analogue of L-carnitine, potentially may improve cardiac function, possibly through a positive inotropic effect. As its hemodynamic profile is unknown in humans, 32 fasting normotensive patients with coronary artery disease received either 15 mg/kg of LPC (n = 16) or vehicle (mannitol/acetate, n = 16) infused over 5 min. Hemodynamic, radionuclide [peak ejection and filling rates (PER and PFR, respectively)], and metabolic variables (myocardial O2, lactate, and carnitine uptake) were studied at baseline and 1, 3, 5, 10, 15, and 45 min postdrug. The baseline ejection fraction was depressed in LPC patients (40 +/- 3% vs. 48 +/- 4% in the vehicle group, p less than 0.05) as a result of a significant high incidence of previous infarctions. Immediately following LPC, the cardiac total carnitine uptake changed from 102 +/- 181 to 5,335 +/- 1,761 mumol/L (p less than 0.05). In both groups, left ventricular systolic and end-diastolic pressures increased significantly by 5 and 20%, respectively, during the first 5 min. In the vehicle group, contractility decreased by 5%, accompanied by a significant 11% fall in the stroke volume. In contrast, following LPC, isovolumetric contractility indices remained unaltered. Instead, both the PER and PFR improved by 16% at 45 min. Moreover, the cardiac output increased by 8%. LPC did not affect systemic or coronary hemodynamics. Lactate uptake increased by 42%, but myocardial O2 consumption did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of the effectiveness of three regimens in the prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) is a major cause of morbidity and the leading cause of death in patients with the acquired immunodeficiency syndrome. The prevention of the occurrence and recurrence of PCP is a cornerstone in the treatment of patients infected with the human immunodeficiency virus. There are few studies comparing PCP prophylactic regimens. METHODS: The efficacy of three regimens for prophylaxis against PCP was assessed in a retrospective chart review of 211 human immunodeficiency virus-infected patients at risk for the disease. Over the course of the 2-year study period, 133 patients were prescribed trimethoprim-sulfamethoxazole (one double-strength tablet twice a day, thrice weekly) for a mean of 7.4 months (range, 1 to 25 months). Seventy-seven patients received dapsone (50 mg daily) for a mean of 5.7 months (range, 1 to 23 months), and 125 patients received aerosolized pentamidine (300 mg via nebulizer once monthly) for a mean of 9.3 months (range, 1 to 21 months). The majority of patients (62%) received primary prophylaxis; 38% had one or more previous episodes of PCP; and 73% were receiving concomitant antiretroviral therapy. RESULTS: Pneumocystis carinii pneumonia did not develop in any patient receiving trimethoprim-sulfamethoxazole in 981 patient-months. Five patients receiving dapsone for 437 patient-months and 17 patients receiving aerosolized pentamidine for 1166 patient-months developed PCP. Fifty-six percent of the trimethoprim-sulfamethoxazole group and 55% of the dapsone group changed drug due to adverse reactions, while only 2% in the aerosolized pentamidine group required drug change. CONCLUSION: Despite its adverse reaction profile, trimethoprim-sulfamethoxazole is the most effective agent to prevent the occurrence and recurrence of PCP.

A quantitative index derived from 99mTc-pertechnetate scintigraphy to assist in the diagnosis of primary Sjögren's syndrome.

A safe and simple technique is reported by which primary Sjögren's syndrome can be detected with a relatively high specificity and sensitivity. The method of serial scintigraphy has been used with reasonable success; however, the application of the linearity index as described here produced superior results. In 71 patients investigated, a sensitivity of 87% and specificity of 93% were recorded and make this the method of choice for evaluating patients suspected of having primary Sjögren's syndrome.

Spectral content as a cue to perceived auditory distance.

Changes in the spectral content of wide-band auditory stimuli have been repeatedly implicated as a possible cue to the distance of a sound source. Few of the previous studies of this factor, however, have considered whether the cue provided by spectral content serves as an absolute or a relative cue. That is, can differences in spectral content indicate systematic differences in distance even on their first presentation to a listener, or must the listener be able to compare sounds with one another in order to perceive some change in their distances? An attempt to answer this question and simultaneously to evaluate the possibly confounding influence of changes in the sound level and/or the loudness of the stimuli are described in this paper. The results indicate that a decrease in high-frequency content (as might physically be produced by passage through a greater amount of air) can lead to increases in perceived auditory distance, but only when compared with similar sounds having a somewhat different high-frequency content, ie spectral information can serve as a relative cue for auditory distance, independent of changes in overall sound level.

Outcomes of treatment with AZT of patients with AIDS and symptomatic HIV infection.

Although many experimental treatments are being evaluated for the treatment of acquired immunodeficiency syndrome (AIDS) and symptomatic HIV infection (ARC), only zidovudine (AZT) has been shown to prolong the lives of such patients. This article reviews the authors' experience with 101 patients with AIDS (73) or ARC (28) treated with AZT at a public hospital clinic in Los Angeles County. The patients were seen at least monthly for five to 87 weeks (means = 27.6) by nurse practitioners and physicians. Initiation of AZT therapy required a CDC-defined diagnosis of AIDS or an absolute CD4 lymphocyte cell count of 200/mm3 or less. The demographic distribution of the patient population was as follows: Caucasian, 59; Hispanic, 22; and black, 20. The mean age of the population was 37.4 years, and the predominant risk factor was homosexual contact (76 percent). Forty-one patients required modification of their AZT doses secondary to anemia, neutropenia, a combination of anemia and neutropenia, or for personal reasons. Thirty-four of the 41 patients (83 percent) never returned to full dose after reductions. The majority of these patients (81 percent) had AIDS and/or CD4 lymphocyte counts less than 150/mm3. Hematologic toxicity was common; 27 percent required blood transfusions. Of the 101 patients followed from five to 87 weeks, 87 percent were surviving after a mean of 45 weeks of AZT therapy. The article underscores the effectiveness of AZT in prolonging the lives of AIDS and ARC patients.

Uterine radiation dose from open sources: the potential for underestimation.

The evaluation of the risk of radiation damage to the unborn child as the result of the administration of radionuclides remains a subject for discussion (Mountford 1989). Lack of information concerning the biodistribution of radiopharmaceuticals in the early stages of pregnancy, before organogenesis has occurred, has greatly restricted the objective assessment of fetal doses. Recent observations on the biodistribution of a therapeutic dose of sodium iodide 131 in a patient with an unsuspected early pregnancy lead us to suspect that current dose estimates with respect to uterine exposure (ARSAC 1988) may seriously underestimate the actual exposure of the developing fetus.

Indium 111 antimyosin for the detection of leiomyosarcoma and rhabdomyosarcoma.

111In-antimyosin monoclonal antibody complex passes through damaged myocardial cell membranes and binds to the intracellular myosin. Normal myocardial and other muscle cells show no uptake. Rhabdomyosarcoma and Leiomyosarcoma cells also contain intracellular myosin and the cell membrane permeability is greater than normal. Significant uptake of 111In-antimyosin was observed in patients with Leiomyosarcoma and Rhabdomyosarcoma suggesting that the reagent has a potential for the in vivo detection of these tumour types. Tumour to background ratios of 10:1 were measured in one case and in view of the fact that the site of accumulation is intracellular, antimyosin may have a potential as a carrier for therapeutic agents.

The stability of 99mTc-DTPA and 99mTc-HIDA following ultrasonic nebulisation.

The stability of 99mTc-DTPA (diethylenetriamine-pentaacetic acid) and 99mTc-HIDA (2,6-diethylacetanilido-iminodiacetic acid) were evaluated following ultrasonic nebulisation. The results confirm that either of these radiopharmaceuticals can be used in our nebuliser without significant radiochemical breakdown.