Prototype algorithm for automated determination of gastric slow wave characteristics.

An algorithm for determining the frequency and propagation time of the gastric slow wave has been designed for integration into a demand gastric pacing system. The algorithm analyses the serosal activity in both the time and frequency domains, and the results are compared to produce a conclusion only when the values are within 5% of each other. Thus, the probability of inappropriate intervention is reduced, at the expense of unidentified segments. The system is verified by comparing the conclusions produced by the algorithm with conclusions from hand analysis of seven canine and one human serosal recordings. The algorithm correctly identifies the slow-wave frequency in the distal portion of the stomach for 90% of the segments, while producing no incorrect results. Slow-wave propagation times in the antrum are correctly identified for 84% of the segments, with no incorrect identifications.

A phase II study of [90Y] yttrium-capromab pendetide in the treatment of men with prostate cancer recurrence following radical prostatectomy.

There is currently no curative therapy for men who have disseminated prostate cancer following failed radical prostatectomy. The purpose of this trial was to investigate systemic radioimmunotherapy in these men. Eight patients with occult metastatic prostate cancer following radical prostatectomy as evidenced solely by a rising serum PSA and evidence of soft tissue lesions outside the prostatic fossa detected by an [111I]indiumcapromab pendetide scan received an infusion of 10 mg of capromab pendetide labeled with 9 mCi/m2 of [90Y]yttrium. Serum PSA was used to measure response rate. There were no complete or partial responses by PSA criteria. Significant unexpected bone marrow toxicity developed in the first 6 of 8 patients treated. The last two patients received co-infusion of edetate calcium disodium in an effort to decrease marrow suppression. In these two patients less marrow toxicity was seen. Repeat 111In-capromab pendetide scans were uninterpretable due to grossly altered whole-body biodistribution of the radioimmunoconjugate. Retrospective analysis of serial PSA values after closure of the study showed a decrease in the log slope PSA for seven of eight patients following radioimmunotherapy, with a statistically significant change in the mean log slope (p = 0.01). The clinical significance of this small but measurable change is uncertain. We conclude that radioimmunotherapy for occult metastatic prostate cancer using 90Y-capromab-pendetide at the dose described does not lower serum PSA, is associated with significant hematologic toxicity, and leads to complexation of the immunoconjugate following subsequent capromab pendetide infusion.

Gastric pacing improves emptying and symptoms in patients with gastroparesis.

BACKGROUND & AIMS: No effective treatment is available for patients with gastroparesis refractory to standard medical therapy. The aim of this study was to investigate the effects of gastric pacing on gastric electrical activity, gastric emptying, and symptoms in patients with gastroparesis. METHODS: Nine patients with gastroparesis participated in this study. Four pairs of cardiac pacing wires were implanted on the serosa of the stomach. The protocol consisted of two portions: a temporary inpatient study period and an outpatient study for a period of 1 month or more. RESULTS: Gastric pacing entrained the gastric slow wave in all subjects and converted tachygastria in 2 patients into regular 3-cpm slow waves. Gastric emptying was significantly improved after the outpatient treatment with gastric pacing. The gastric retention at 2 hours was reduced from 77.0% +/- 3.3% to 56.6% +/- 8.6% (P < 0.05). Symptoms of gastroparesis were substantially reduced at the end of the outpatient treatment (1.51 +/- 0.46 vs. 2.84 +/- 0.61; P < 0.04). Eight of 9 patients no longer relied on jejunostomy tube feeding, and no adverse events were noted related to the pacing unit. CONCLUSIONS: Gastric pacing seems to be able to improve symptoms of gastroparesis and to accelerate gastric emptying in patients with gastroparesis. More controlled studies are necessary to further investigate the role of gastric pacing in clinical practice.

Adenocarcinoma of the prostate: innovations in management.

Adenocarcinoma of the prostate (CaP) in the Western world has become the most common noncutaneous human tumor. CaP is also the second most important cause of cancer deaths among the male population in the United States. Major progress was made in the past decade in better understanding this disease process, as well as in improved diagnostic accuracy. This improved diagnostic accuracy was due to wide application of prostate-specific antigen (PSA), use of transrectal ultrasound (TRUS), and greater awareness among clinicians of CaP. The use of PSA in clinical practice has resulted in a sharp increase in the number of patients diagnosed with capsule-confined tumors. The optimal treatment for capsule-confined CaP is in the process of being defined. Radical prostatectomy in the United States is currently the most commonly applied treatment for younger patients. Excellent treatment results with a 10-year actuarial survival > 80% are readily obtainable in properly selected patients. Nerve-sparing procedures helped reduce the high incidence of impotence that occurs in patients after radical retropubic prostatectomy. Radiotherapy remains the other curative treatment method in the management of CaP patients, with long-term survival rates similar to those reported in surgical series. Due to the problem of frequent preoperative tumor understaging, a routine use of postoperative irradiation to the prostatic fossa produces an excellent (> 95%) incidence of local tumor control. Management of patients with metastatic disease has undergone a considerable evolution with the development of modern hormonal management and treatment with strontium-89 to control intractable bone pain. Newer treatment methods such as hyperthermia are currently being investigated. Major efforts are directed toward the reduction of short- and long-term treatment toxicity associated with surgery, radiotherapy, and hormonal management, thus improving patient quality of life.

Regional chemotherapy using continuous intravesical infusion doxorubicin for the treatment of muscle invasive transitional cell bladder carcinoma in a rat model.

Previously established animal models of invasive transitional cell bladder carcinoma and continuous infusion intravesical drug delivery were combined to evaluate the urothelial toxicity and antineoplastic efficacy of continuous intravesical infusion doxorubicin (DOX). Dose-response toxicity experiments studied histologic changes in the rat urinary bladder following urothelial exposure to three different urinary levels of DOX, as a function of the duration of drug infusion. Systemic and local drug absorption, as measured by DOX levels in serum, bladder, retroperitoneal lymph nodes, and liver, was measured at intervals during drug administration. In vitro chemosensitivity assays were used to determine tumor sensitivity to DOX. Treatment studies evaluated the impact of 14-day continuous infusion DOX beginning seven days following tumor implantation. No histologically discernable changes in the normal urothelium were noted in bladders of animals receiving continuous intravesicle DOX at mean urinary concentrations of 0.05 micrograms./ml. (n = 5), 0.56 micrograms./ml. (n = 10), and 5.69 micrograms./ml. (n = 10) for periods of up to 14 days. Serum drug concentrations demonstrated a non-significant upward trend following the start of therapy. Significant increases in tissue DOX levels were noted in the bladder and retroperitoneal lymph nodes on chemotherapy days 7 and 14. Mean tissue DOX concentrations in both the bladder and lymph nodes were greater than the IC50 observed in the in vitro sensitivity assay. DOX-treated tumor-bearing animals (n = 17) had a mean tumor volume (+/- standard deviation) of 0.65 gm. +/- 0.52 gm. compared to an average tumor volume of 1.20 gm. +/- 0.66 gm. in the control group (n = 18) (p = 0.0112). Continuous infusion intraluminal chemotherapy demonstrated a clear cytoreductive effect with minimal local toxicity in this model. Drug tissue levels were observed in regional lymphatic drainage fields as well as the bladder wall. Further study to evaluate this approach as a bladder-sparing alternative to muscle invasive disease is warranted.

Assessment of renal preservation by phosphorus-31 magnetic resonance spectroscopy: in vivo normothermic blood perfusion.

To evaluate the usefulness of the monophosphate/inorganic phosphate ratio (MP/Pi) in assessing renal viability in a renal transplantation setting, we monitored intracellular phosphorous metabolites of 33 canine kidneys by phosphorus-31 magnetic resonance spectroscopy (MRS) after various amounts of ischemia. Renal viability (adequate perfusion and function) was directly assessed by the presence of intraoperative urine production in each kidney. Twelve normal, well-perfused kidneys (Group 1) exhibited high control MP/Pi ratios, with a mean of 0.87 +/- 0.12. Six in situ kidneys (Group 2), subjected to 45 minutes' warm ischemia followed by reperfusion, had a mean MP/Pi ratio of 0.50 +/- 0.12 after warm ischemia, which increased by a mean of 0.50 +/- 0.11 (to 1.0 +/- 0.07) after two to four hours of reperfusion. Fifteen kidneys (Group 3) were removed, cold-flushed and transplanted after 24 hours of hypothermic storage. In eight (Group 3A), reperfusion was excellent; in seven (Group 3B), reperfusion was inadequate secondary to hypotension in two, hemorrhage in two, and renal vein thrombosis in three. Group 3A kidneys had a mean MP/Pi ratio after cold-storage ischemia of 0.54 +/- 0.08. After successful transplantation and two to four hours of reperfusion, this increased by a mean of 0.23 +/- 0.12 to 0.77 +/- 0.15. Group 3B kidneys all showed a continuous decline of MP/Pi, with a mean loss of 0.26 +/- 0.09 from baseline values (mean 0.56 +/- 0.08) to nonviable levels of 0.28 +/- 0.12 within four hours of transplantation. We conclude that MP/Pi ratios enable assessment of renal viability and ischemic damage and can predict the efficacy of renal preservation maneuvers in the dog kidney. These preliminary data support the theory that MRS can be applied to the noninvasive assessment of viability in ex vivo, cold-stored cadaveric human kidneys awaiting renal transplantation.

Enzymology of long-chain base synthesis by aorta: induction of serine palmitoyltransferase activity in rabbit aorta during atherogenesis.

Serine palmitoyltransferase [EC 2.3.1.50] initiates the biosynthesis of sphingolipids by catalyzing the condensation of a fatty acyl-CoA with serine to yield the committed intermediate 3-ketosphinganine or one of its homologues. The presence of serine palmitoyltransferase in aorta was established under optimal assay conditions using microsomes from New Zealand White rabbits. Its activity was dependent on microsomal protein, L-serine, pyridoxal 5'-phosphate, and palmitoyl-CoA. Although several different saturated and unsaturated fatty acyl-CoA thioesters were utilized as substrates, maximal activity was with palmitoyl-CoA, suggesting that this enzyme contributes to the predominance of 18-carbon long-chain bases in sphingolipids from aorta. Rabbits, fed a Purina lab chow supplemented with 2% cholesterol, were used to study serine palmitoyltransferase activity in aorta during experimental atherogenesis. An increase in activity from intimal-medial preparations was detectable prior to prominent lipid accumulation or cellular proliferation. Activity continued to elevate over the 12-week duration of feeding concurrent with the increase in serum cholesterol and in proportion to the development of plaques resulting in a 3.7-fold increase in activity (20.7 +/- 2.6 pmol per min per mg microsomal protein +/- SE in the cholesterol-fed group versus 5.6 +/- 1.9 in the pair-fed controls also matched for age and sex; P less than 0.005). Thus, the accumulation of sphingomyelin that occurs in aorta during experimental atherogenesis may be related to increased long-chain base synthesis by serine palmitoyltransferase.

Assessment of renal viability by phosphorus-31 magnetic resonance spectroscopy.

To assess the applicability of phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in the analysis of renal transplant viability and preservation techniques with respect to pre-transplant ischemia, we studied two rat groups. Twenty-five rat kidneys were subjected to various time increments of warm ischemia (Group A), and 31P-MRS was performed on each kidney at time intervals of up to 72 hours during simple hypothermic storage. We correlated findings of 31P-MRS with simultaneous findings of electron microscopic (EM) ultrastructural viability parameters (in Group A) and subsequent survival and renal function in 30 rats (Group B) subjected to similar amounts of variable ischemia. Intracellular phosphorus metabolite levels were nondestructively monitored by 31P-MRS via spectral peaks of NAD, sugar monophosphates (SP), and inorganic phosphate (Pi). We concluded: SP/Pi and NAD/Pi ratios decay in a time-dependent manner for both warm and cold ischemia, although this process is much slower during cold storage; EM viability parameters correlate with the development of acute tubular necrosis (irreversible damage) versus nonviability (gross cell death) on a qualitative basis only; and 31P-MRS enables a quantitative assessment of renal viability and ischemic renal damage and can predict the degree of acute tubular necrosis and post-ischemic renal function. 31P-MRS is potentially a noninvasive, nondestructive method of assessing viability during simple hypothermic storage of the rat kidney. Preliminary evidence shows that this MRS method can be applied to human kidney viability studies for clinical renal transplantation and urologic research concerning renal preservation.

Radioimmunoassay of serum prostatic acid phosphatase after prostatic massage.

The effect of prostatic massage on the concentration of prostatic acid phosphatase (PAP) in blood serum as determined by radioimmunoassay (RIA) was compared with that determined by a standard enzymatic assay (EA). Serum was drawn from 24 men before prostatic massage and after--at specified intervals, up to twenty-four hours. Three of these men were young, normal controls; 10 had biopsy-proved prostate cancer (CA); 11 had histologically confirmed benign prostatic hyperplasia (BPH). After prostatic massage, 3 of the 10 CA patients (30%) had elevation of PAP as determined by EA and 4 of the 11 BPH patients (36%) as determined by RIA. None of the controls showed elevated levels of PAP by either assay. In all patients elevated levels of PAP by both assays had returned to normal twenty-four hours after massage. It was concluded that serum for PAP testing by either assay method should be drawn before or twenty-four hours after rectal examination to prevent false positive results and the need for retesting.

Urolithiasis in patients with a jejunoileal bypass.

Five hundred and seventeen patients who had a jejunoileal bypass performed at the University of Minnesota Hospitals were studied with regard to the formation of urinary calculi postoperatively. A 9 per cent incidence of stones was found in the 365 patients for whom complete data were available. Men were affected more commonly than women. Of particular note was the correlation between long term oral supplementation of calcium postoperatively and a delay in the onset of symptomatic urolithiasis. A group of 91 recent patients who have been maintained on orally administered calcium are stone-free as long as 12 months after operation, again suggesting that supplementation of calcium may help prevent urolithiasis in patients who have had a bypass procedure.