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Biomedical subjects

J B Regan

Publications and source records attributed to J B Regan.

At least 19 recordsLinked to original sources

A new temporary catheter (ContiCath) for the treatment of temporary, reversible, postoperative urinary retention.

OBJECTIVES: To describe the initial experience of a newly designed temporary urethral catheter, ContiCath, as an aid in the management of postoperative or temporary outflow obstruction. In patients with normal detrusor and sphincter function, this catheter allows volitional voiding while maintaining an open prostatic urethra. METHODS: In a pilot study, 64 nonconsecutive patients with postoperative or temporary urinary retention, at eight clinical trial sites, were enrolled for the placement of this temporary catheter. Three patients did not have the catheter placed because of placement failure because of either a large median lobe or a urethral stricture. The remaining 61 patients were divided into three groups: those with non-neuropathic causes of retention and retention for 1 week or less (37 patients), those with non-neuropathic causes of retention and retention for longer than 1 week (19 patients), and those with neuropathic causes of retention and retention for longer than 1 week (5 patients). The ContiCath is placed in the office setting, in the same fashion as a Foley catheter. A blue prolene tether extends from the bulbar urethra to the meatus to assist in the removal of the device. Patients were then reassessed at 3 hours, and at 7, 14, 21, and 28 days, at which point the device was removed. RESULTS: In patients with a neuropathic cause for their retention (5 patients) and those with non-neuropathic causes of retention and retention for longer than 1 week (19 patients), only 3 patients were able to void after the catheter was placed. Of the 37 patients with a non-neuropathic cause and retention 1 week or less, controlled voiding was seen in 33 patients (89%). Controlled voiding was defined as the patient's volitional ability to initiate and stop his urinary stream. There were no complications with catheter placement; however, 8 patients (24.2%) had minor adverse experiences of frequency/urgency (n = 3), incontinence (n = 3), migration of the catheter (n = 1), and pain (n = 1). CONCLUSIONS: ContiCath offers an alternative to an indwelling Foley catheter in men with temporary bladder outlet obstruction and urinary retention.

Aged↗

Ureteritis cystica with 17-year followup.

Ureteritis cystica is a rare disease that must be considered in the differential diagnosis of ureteral and renal pelvic filling defects. The characteristic radiographic findings often regress spontaneously when the process instigating the inflammation is eradicated. However, in our patient radiological findings remained unchanged during a 17-year period in the absence of malignancy or infection. Although it sometimes coexists with cancer, we believe that ureteritis cystica is usually benign and indolent.

Aged↗

Transurethral microwave thermotherapy for management of benign prostatic hyperplasia: results of the United States Prostatron Cooperative Study.

The primary objective of the study was to determine the safety and efficacy of transurethral microwave thermotherapy for the treatment of symptomatic benign prostatic hyperplasia. From March to August 1991, 150 patients were entered into a multi-site study and treated with transurethral microwave thermotherapy under a Food and Drug Administration approved protocol. Only patients with symmetrical trilobar or bilobar prostatic hypertrophy, peak flow rate of less than 15 cc per second (on 2 voided volumes of 150 cc or greater) and a total Madsen symptom score of more than 8 were treated. Transurethral microwave thermotherapy was performed with a 20F catheter and 1,296 MHz. microwave antenna for 60 minutes. The mean power achieved for this single session was 32.1 watts, with a mean power at maximum urethral temperature of 41.1 watts. Mean urethral temperature was 44.3C and the mean rectal temperature was 42.2C. The rectal and urethral temperatures were continuously monitored. Mean peak urinary flow rates, Madsen symptom score, post-void residual volume and improvement in motivating symptom to seek treatment were measured at 6 weeks, and 3, 6 and 12 months. Mean peak urinary flow rates improved 33% at 12 months (p < 0.0001). Overall, the mean Madsen symptom score improved 61% (p < 0.0001). The obstructive score and the irritative score improved 67% and 43%, respectively. Of 17 patients 12 (71%) reported improvement in weak stream when that was the motivating symptom to seek treatment. Of 28 men 18 (64%) reported improvement in nocturia, while 11 of 30 (37%) reported improvement in daytime frequency and 12 of 17 (71%) reported improvement in urgency. There was no statistically significant difference in post-void residual volume at 12 months from baseline. The treatment was well tolerated by all patients, and side effects were considered mild and transitory. Our study demonstrates the safety, effectiveness, patient tolerability and durability of transurethral microwave thermotherapy.

Adult↗

The synthesis of alternating alpha,beta-oligodeoxyribonucleotides with alternating (3'-->3')- and (5'-->5')-internucleotic linkages as potential therapeutic agents.

A simplified synthesis of alpha-2'-deoxyribonucleoside derivatives has been developed and the solid-phase preparation of antisense alpha,beta-oligodeoxyribonucleotides with alternating (3'-->3')- and (5'-->5')-internucleotidic phosphodiester linkages, targeted against HIV-1 tat mRNA, has been accomplished. Hybridization properties of these oligonucleotide analogues have been investigated.

Base Sequence↗

Spectrum of renal vascular malformation.

In summary, renal AVMs are rare. The possibility of these lesions should be raised in cases of hematuria of unknown etiology, prolonged hematuria following trauma or needle biopsy, unexplained congestive heart failure or abdominal/flank bruit, or hypertension after renal trauma. Selective renal arteriography is the study of choice for establishing the diagnosis, the hallmark being demonstration of an abnormal arterial communication with a vein. The goal of management should be maximum preservation of renal parenchyma. Observation with follow-up is indicated for asymptomatic AVMs.

Adult↗

Oligodeoxyribonucleoside methylphosphonates. NMR and UV spectroscopic studies of Rp-Rp and Sp-Sp methylphosphonate (Me) modified duplexes of (d[GGAATTCC])2.

1H NMR chemical shift assignments for the title compounds were made for most of the 1H signals using two-dimensional nuclear Overhauser effect (2D-NOE) data, which were also used to establish the absolute configuration at the modified phosphorus. The chemical shifts were similar to those reported [Broido, M.S., et al. (1985) Eur. J. Biochem. 150, 117-128] for the unmodified, parent, B-type duplex [d(GGAATTCC)]2. Differences in chemical shifts were mostly localized to the nucleotides on the 5'- and 3'-sides of the modified phosphorus. The Rp-Rp isomers exhibited UV-derived Tm values similar to that of the parent duplex. On the other hand, the Sp-Sp isomers generally exhibited lower Tm values which correlated with P-CH3--H3' (n-1 nucleotide) cross peak intensities and 31P spectral parameters. The combined data argue for increased steric interactions with the Sp-P-Me methyl group as the modification position is moved toward the center of the oligomer. All of the Tm results can be explained in terms of three factors which result from replacement of a phosphate by a methylphosphonate group: reduction of oligomer charge; electronic and other substituent effects; steric interactions.

Deoxyribonucleosides↗

NMR spectroscopic studies of intermediary metabolites of cyclophosphamide. 2. Direct observation, characterization, and reactivity studies of iminocyclophosphamide and related species.

4-Hydroxy-5,5-dimethylcyclophosphamide (6) was synthesized as a stable (to fragmentation) analogue of 4-hydroxycyclophosphamide (1). In anhydrous Me2SO-d6 (less than or equal to 0.03 mol % water), cis- and trans-6 were observed by multinuclear NMR spectroscopy to equilibrate with alpha, alpha-dimethylaldophosphamide (7) and 5,5-dimethyliminocyclophosphamide (8). Identification of 8 was based on 1H, 13C, and 31P chemical shifts, selective INEPT and two-dimensional NMR correlation experiments, and temperature-dependent equilibria data. The interconversion of cis-/trans-6 and -7 was also observed in lutidine buffer; 8 was not detected under the aqueous conditions. In Me2SO-d6, hydroxy metabolite 1 underwent dehydration to give iminocyclophosphamide (5), as evidenced by chemical shift data and a selective INEPT experiment. Concentrations of cis-/trans-1, aldophosphamide (2), and 5 were found to be temperature-dependent with higher temperatures favoring 2 and 5 in a reversible manner, thus indicating that 1/2/5 were intercoverting. The addition of small amounts of water to Me2SO-d6 solutions of imine 5 resulted in the immediate disappearance of its NMR signals. The role of imine 5 in the conversion of 1 to C-4 substituted analogues of 1 was elucidated for the formation of 4-cyanocyclophosphamide (3a) from 1 and sodium cyanide in lutidine buffer.

Cyclophosphamide↗

Giant leiomyoma of the prostate.

Giant leiomyoma of the prostate is a rare lesion. We document a case in a 61-year-old man who presented with urinary obstructive symptoms. He had undergone transurethral resection twice before he was seen at our institution, where suprapubic prostatectomy was performed. At follow-up 18 months postoperatively, no evidence of recurrent disease was found and his voiding pattern was normal.

Humans↗

Alkyl phosphotriester modified oligodeoxyribonucleotides. V. Synthesis and absolute configuration of Rp and Sp diastereomers of an ethyl phosphotriester (Et) modified EcoRI recognition sequence, d[GGAA(Et)TTCC]. A synthetic approach to regio- and stereospecific ethylation-interference studies.

Protected deoxynucleoside 3'-O-ethyl-N,N-diisopropylphosphoramidite reagents were prepared for use in the automated synthesis of ethyl phosphotriester (Et) modified oligonucleotides. The title diastereomers were separated by reversed-phase HPLC, and chirality at phosphorus was assigned by an improved configurational correlation scheme that was verified by NMR spectroscopic studies (accompanying paper, Part VI). This generally applicable correlation scheme involved enzymatic digestions of each diastereomer to give the corresponding diastereomer of d[A(Et)T]; phosphite triester sulfurization to obtain diastereomeric O-ethyl phosphorothioates, d[AS(Et)T], which were separated by HPLC for stereoretentive oxidation with H2O2 to give d[A(Et)T], and stereoretentive de-ethylation with PhSH-Et3N to give diastereomeric phosphorothioates, d[AST], whose configurations at phosphorus had been assigned previously. Neither the Rp-Rp nor Sp-Sp duplex, (d[GGAA(Et)TTCC])2, was cleaved by EcoRI endonuclease under conditions that led to cleavage of both the unmodified duplex, [d(GGAATTCC)]2, and the mixture of diastereomeric phosphorothioate-modified duplexes, [d(GGAASTTCC)]2. Cleavage of the latter substrates was Sp-selective.

Base Sequence↗

Congenital renal arteriovenous malformations.

Congenital arteriovenous malformations are rare lesions of the kidney. We evaluated the clinical course of 15 patients with this lesion who were seen between 1950 and 1984. There were 9 women and 6 men, and the median age at diagnosis was 48 years. Patients presented most commonly with hematuria (93 per cent) or hypertension (53 per cent). Of the 15 patients 10 underwent nephrectomy because of gross hematuria or the perceived risk of significant bleeding, or in an effort to control hypertension. None of the 10 patients has required a further operation and those who were hypertensive preoperatively remained hypertensive postoperatively. The remaining 5 patients were treated conservatively, either with observation or antihypertensive medications. All 5 patients had microscopic hematuria and none has required further therapy. It would seem that neither microscopic hematuria nor controlled hypertension is an indication alone for nephrectomy.

Adolescent↗

Synthesis and antitumor activity of cyclophosphamide analogues. 4. Preparation, kinetic studies, and anticancer screening of "phenylketophosphamide" and similar compounds related to the cyclophosphamide metabolite aldophosphamide.

Phenyl ketone phosphorodiamidates [C6H5C(O)CH2CH2OP(O)NHR1NR2R3] were synthesized in conjunction with an ongoing investigation into the effects of substituents on the dynamical solution chemistry of the metabolites of cyclophosphamide (1a). In contrast to aldophosphamide (3a), which readily interconverts with its cyclic isomer 4-hydroxycyclophosphamide (2a), phenylketophosphamide (14a: R1 = H, R2 = R3 = CH2CH2Cl) exhibited an apparent "resistance" toward an intramolecular addition reaction such that 4-hydroxy-4-phenylcyclophosphamide (13a) could not be detected either spectroscopically (31P or 13C NMR) or chemically (NaCN trapping experiment). Control studies that compared the relative reactivities of 14a and methylketophosphamide [20: CH3C(O)CH2CH2OP(O)NH2N-(CH2CH2Cl)2] revealed that the factors that modulate the ring closure/opening reactions were not peculiar to the phenyl group; however, differences between phenyl and methyl profoundly influenced the rates of fragmentation of 14a and 20. 31P NMR spectroscopy was used to determine the rates at which each compound generated a cytotoxic alkylating agent. Under a standard set of reaction conditions [1 M lutidine buffer with added Me2SO (8:2), pH 7.4, 37 degrees C], the half-lives of 2a/3a, 14a, phenylketoifosfamide (14b: R1 = R2 = CH2CH2Cl, R3 = H), phenylketotrofosfamide (14c: R1 = R2 = R3 = CH2CH2Cl), and 20 were 72, 66, 63, 56, and 173 min, respectively. Analogues 14a and 14b exhibited good anticancer activity against a variety of test systems.

Animals↗

Synthesis of reactive metabolite-analogues of cyclophosphamide for comparisons of NMR kinetic parameters and anticancer screening data.

Ozonolysis of compounds with the general structure CH2 = CHR1CHR2CH2OP(O) (NHR3)NR42 gave, in each case, one major product which was an analogue of the cyclophosphamide (CP) metabolites aldophosphamide (AP) or 4-hydroxy-CP. 31P NMR spectra recorded for each of these compounds in aqueous buffered solutions at pH 7.4, 37 degrees C, revealed a cascade of reactions similar to those observed for AP and/or 4-hydroxy-CP, although the individual rate constants for these reactions were substituent-dependent. Aryl ketone analogues of AP did not give rise to detectable amounts of their cyclic hemiaminals, but those which produced phosphoramide mustards at rates similar to that found for AP were active against L1210 lymphoid leukaemia in mice. The results indicated that oncostatic selectivity may not require cell-specific oxidative detoxification.

Animals↗

Childhood otitis media with effusion: six-year follow-up.

Twenty-five patients were re-evaluated six years after presenting with their first episode of otitis media with effusion. The average age at presentation was 6.2 years. Twenty-three were found on follow-up to have normal audiometry and tympanometry, and had improved or at least remained stable in school performance. Recurrences of acute middle ear disease were noted during follow-up in eight of the patients, specially among the six who had presented in the summer, and more frequently among the eight children who eventually had tympanostomy tubes placed. This study appears to support the concept that otherwise normal American children presenting with otitis media with effusion seem fairly uncommonly to develop severe, recurrent middle ear disease.

Acoustic Impedance Tests↗

Stented versus nonstented ureteroileal anastomoses: is there a difference with regard to leak and stricture?

We reviewed the clinical histories of 362 patients (711 renal units) who had undergone ileal conduit diversion. Stents were used in 126 patients (247 renal units) and were not used in 236 (464 renal units). The stented group was divided further into 95 patients (186 renal units) with silicone single J stents and 31 (61 renal units) with some other type of stent. The over-all incidence of urine leakage was 1.7 per cent (6 of 362 patients). The over-all incidence of stricture was 3.9 per cent (11 without and 3 with stents). No leak occurred among the 126 patients in whom a stent was used. None of the 95 patients in whom silicone single J stents were used had stricture. If stents are to be used, we recommend silicone single J stents because of their satisfactory performance to date.

Female↗

Childhood serous otitis media: fifteen months' observations of children untreated compared with those receiving an antihistamine-adrenergic combination.

Of 55 patients who had received, in a previously reported double-blind study, either an antihistamine-adrenergic combination or a placebo for three months for serous otitis media, 48 were followed without drug therapy for an additional year. During the follow-up period no differences were detected between the patients who had initially been treated with drugs and those who had received the placebo, as detected by audiometry, tympanometry, parental concern about hearing loss (as detected by the parents themselves or by their children's teachers or primary health care providers), school performance, or recurrences of serous otitis media.

Child↗