Biomedical subjects
Publications and source records attributed to R Maguire.
Enantiopure L-azetidine-2-carboxylic acid, the (3R)-phenyl, (3R)-naphthyl and (3S)-isopropyl analogs were prepared based on a zinc-mediated asymmetric addition of allylic halides to the camphor sultam derivative of glyoxylic acid O-benzyl oxime.
BACKGROUND: Optimum therapy for prostate carcinoma patients requires accurate staging, but computed tomography (CT) and magnetic resonance imaging (MRI) have limitations as methods for detecting soft tissue metastases. In this study, radioimmunoscintigraphy (RIS) was evaluated for its ability to identify sites of metastatic disease in lymph nodes. METHODS: RIS was evaluated in 51 prostate carcinoma patients at high risk for metastatic disease. An intravenous infusion of indium-111 capromab pendetide was given, followed by nuclear medicine imaging on two separate dates. Bilateral, open pelvic lymph node dissection was performed with additional exploration and biopsy of scan positive extraprostatic regions. Histologic evaluation of removed tissue confirmed the accuracy of RIS. In addition, results were compared with other standard methods for diagnosing patients prior to surgery. RESULTS: Nineteen patients (37%) had evidence of lymph node involvement with RIS. Fifteen of the 19 positive patients had pathologic evidence of cancer in the biopsied lymph nodes. Sensitivity, specificity, accuracy, and the positive predictive value for detection of extraprostatic disease were 75%, 86%, 81%, and 79%, respectively. CT, MRI, and ultrasound of the pelvis demonstrated a combined accuracy of only 48% in detecting lymph node disease. Twenty-five previously undetected sites were deemed positive with RIS. Fourteen of these were biopsy-proven tumor sites, seven were probable tumor sites, and four were assumed to be false-positive. CONCLUSIONS: RIS had an impact on patient management through its detection of occult disease in more than 50% of prostate carcinoma patients studied, and it provided information concerning the likelihood that lymph node metastases would be found during surgery.
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Over a 12 month period, we prospectively evaluated the use of an ambulatory infusion pump for intra-arterial and intravenous chemotherapy in patients with colorectal liver metastases. In all, 274 separate infusions were given with minor complications occurring on six occasions. Administering treatment on an outpatient basis rather than as an inpatient has resulted in savings of over Pounds 17000 in the first year.
Six females suffering from Multiple Sclerosis (MS) with symptoms of constipation and faecal incontinence were investigated using anal manometry, proctometrogram, proctography and large bowel transit time estimates (using inert markers). Results were compared to a control group (4 females, 2 males). Resting anal sphincter pressure (internal sphincter function) was reduced, but not significantly so, compared with controls (46 +/- 12.6 vs. 68 +/- 8.2 mm Hg: P < 0.1). Maximum squeeze increment pressure (external sphincter function) was significantly diminished in the patient group (13.5 +/- 4.5 vs. 82.5 +/- 12.3 mm Hg: P < 0.0001). Radiological imaging of the anorectum demonstrated an abnormal position of the pelvic floor at rest, with moderate descent in most cases during straining. Measurement of anorectal angles (puborectalis muscle function) indicated a normal angle at rest (76 +/- 10.4 degrees), but with little change on maximum contraction (74 +/- 3.5 degrees) and on straining (79 +/- 4.6 degrees). Rectal sensory parameters did not differ from controls either for minimum sensation, 44.5 +/- 5.2 vs. 30 +/- 5.8 ml (P < 0.1), or at maximum tolerable volume, 163 +/- 34.5 vs. 148 +/- 22 ml (P > 0.2). Four of six patients failed to empty 100% of simulated stool at proctography, at which the only anatomical defect was the presence of a rectocele in two patients. Large bowel transit studies revealed abnormally slow transit in 82% of patients, all of whom had delay in the distal colon. These physiological studies demonstrate that in patients with MS who had anorectal dysfunction, there is a marked impairment of external anal sphincter function with moderate changes in pelvic floor musculature.(ABSTRACT TRUNCATED AT 250 WORDS)
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Wy 18,251 (Tilomisole; Wyeth Laboratories, Philadelphia, PA, USA) is a benzimidazole that is structurally similar to the antihelminth levamisole that has recently been approved for the adjuvant treatment of colon cancer. In preclinical models, Tilomisole caused less agranulocytosis than levamisole, but retained immunomodulating capabilities. We examined the effects of Tilomisole administered to cancer patients in four different dose schedules: 60 mg/m2 orally (p.o.) weekly, and 60, 300, or 960 mg/m2 p.o. daily for 1 month. All patients were immunosuppressed when treatment was initiated as defined by standardized assays of phytohemagglutinin, concanavalin A, pokeweed mitogen, and mixed lymphocyte responses. Tilomisole was well tolerated with no significant side effects in 25 patients. There were no antitumor responses noted in this setting of metastatic cancer. There was no improvement in concanavalin A or pokeweed mitogen assays at any dose or schedule, but there was sustained improvement in mixed lymphocyte reaction and phytohemagglutinin assays at the 60 mg/m2 daily dose. This drug may have favorable biological response modifying effects in vivo and be a suitable alternative to levamisole in cancer treatment, especially if agranulocytosis is a significant problem associated with widespread use of levamisole.
We preview the results of the first year in a Miscarriage Clinic set up in 1989 in an effort to improve the support and counselling of women who have a miscarriage. Of 381 patients referred, 79% attended. The only statistically significant difference between the women who attended and those who did not attend was in the proportion of women who had planned their pregnancies (65% versus 33%, P less than 0.01). Of the 300 patients who attended, 4% reported no grief reaction; 75% experienced a reaction which had resolved within one month and 21% experienced a reaction which had not resolved. No factor was identified which could predict the duration of the grief reaction. This audit demonstrates that there is a strong demand and need for this service for couples who experience a miscarriage.
In a retrospective study of the period 1982-1985, the records of 29 narcotic-addicted mothers and their 42 babies were reviewed. All mothers were from socially deprived backgrounds, had a poor record of ante-natal attendance and had frequent admissions to hospital. Thirteen mothers had a past history of hepatitis B and four were HBsAg positive. The babies had significantly lower mean gestational age and mean birth weight than the control group. Features of withdrawal were recorded in 84% of babies where a history was available. A high incidence of twins (10.5%) was also observed. Testing for HIV antibody in more recent cases has revealed positive results in seven mothers and three babies; one infant has since died from acquired immune deficiency syndrome.
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As part of an investigation of the cellular origins of undifferentiated lymphomas of the Burkitt's and non-Burkitt's types, we have examined immunoglobulin secretion by cell lines and biopsy samples from these tumors and have compared it with other lymphoblastoid cell lines. The majority of American lymphoma cell lines and a smaller fraction of African lymphoma cell lines secreted monoclonal IgM. No other Ig classes were secreted. Ig secretion by the tumor samples was also found to be exclusively IgM. The secreted IgM was polymeric and associated with J chain. Secretion of free light chain by most of the tumor cell lines was observed. Quantitation by immunoassay demonstrated that the American lymphoma cell lines secreted significantly more IgM than the African lymphoma cell lines. We have proposed that the lymphoma cells represent an early stage of B cell differentiation, during which antigen-independent secretion occurs.
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The classical radiologic manifestations of Wegener's granulomatosis are paranasal sinus disease and pulmonary nodules. A review of 31 clinicopathologically proven cases of Wegener's granulomatosis was undertaken to delineate some of the atypical radiologic presentations in this disorder. In 16 of the 31 patients a total of 18 atypical radiographic findings were demonstrated. These included lesions of the airways, parenchyma, pleura, and kidneys. We feel the "typical radiologic findings" of Wegener's granulomatosis should be expanded to include (1) endobronchial disease resulting in atelectasis of either a lobe or a complete lung, and (2) pleural disease with thickening or effusion which may be massive. While some of the rarer presentations are still not included, such a redefinition would cover more than 75% of our 31 cases.
Partial Budd-Chiari syndrome was produced in 8 monkeys by obstructing 2 or 3 lobar hepatic veins with a rapidly polymerizing plastic. Hepatic angiography done 1-3 months later revealed crowded tortuous arteries and a dense hepatogram in the lobe with venous occlusion. Unobstructed lobes were hypertrophied. Retrograde injection of persistently patent hepatic veins demonstrated a "spiderweb" collateral system. Retrograde venography to demonstrate this pathognomonic plexus is the procedure of choice when partial Budd-Chiari syndrome is suspected.
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