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Biomedical subjects

J W Roberts

Publications and source records attributed to J W Roberts.

At least 55 records · Page 3Linked to original sources
PubMed1993

Laparoscopic-assisted bowel surgery.

The use of laparoscopic surgical techniques is now being applied to a variety of operations traditionally performed in an open fashion. Twenty patients underwent laparoscopic-guided large and small bowel surgery at our institution from March 1991 to April 1992. The indications for surgery included polyps, obstruction, bleeding, and perforation, and pathologic diagnoses included benign polyps, lipomas, inflammatory bowel disease, perforation of a jejunal diverticulum, colonic arteriovenous malformations, and adenocarcinoma. Mobilization of the colon, ligation of the mesentery, and closure of the mesenteric defect were performed using the laparoscopic equipment. One trocar site was enlarged to 3 cm to deliver the bowel through the abdominal wall. All anastomoses were hand-sewn. Postoperative hospitalization ranged from 2 to 31 days (median, five days). No mortality was noted, and morbidity was 20 percent. We conclude that laparoscopic-guided bowel surgery is technically feasible and should translate into shorter hospitalization and less patient discomfort.

Aged↗
PubMed1993

End-of-dose dystonia in Parkinson's disease.

To evaluate the pathogenesis of end-of-dose dystonia in levodopa-treated patients with Parkinson's disease, we discontinued a steady-state optimal-dose levodopa infusion either abruptly or slowly. Although dystonic signs appeared sooner after sudden levodopa termination, in both situations dystonia emerged only when circulating drug levels had fallen to the same concentration and parkinsonian scores had declined by the same amount. Dystonia onset thus appears to reflect the degree, rather than the rate, of reduction in dopaminergic stimulation, and may involve the preferential interaction of dopamine with a receptor subpopulation that does not mediate its antiparkinsonian efficacy.

Adult↗
PubMed1993

Catechol-O-methyltransferase inhibitor tolcapone prolongs levodopa/carbidopa action in parkinsonian patients.

The wearing-off phenomenon frequently complicates levodopa therapy of Parkinson's disease (PD). These response fluctuations appear when intrasynaptic dopamine concentrations begin to reflect the swings in levodopa availability that attend standard dosing regimens. Drugs that prolong the biologic half-life of levodopa and dopamine should thus prove beneficial. We administered levodopa/carbidopa in combination with single oral doses of tolcapone (Ro 40-7592), an inhibitor of catechol-O-methyltransferase, under controlled conditions to 10 PD patients with the wearing-off phenomenon. Tolcapone prolonged the antiparkinson response to levodopa/carbidopa by about 67% at several doses ranging from 50 to 400 mg (p < 0.05). There was no significant change in the peak levodopa effect on parkinsonian signs or in the severity of dyskinesias. No dose-limiting adverse effects occurred. Multiple daily dosing with tolcapone would thus be expected to safely reduce the wearing-off phenomenon associated with levodopa/carbidopa therapy.

Adolescent↗
PubMed1993

Use of Prograf (FK 506) as rescue therapy for refractory rejection after liver transplantation. US Multicenter FK 506 Liver Study Group.

This report describes the clinical characteristics and demographics of patients enrolled into this rescue trial for patients experiencing refractory rejection after liver transplantation. Actuarial graft and patient survival at 12 months postconversion was 50% and 72%, respectively. Actual treatment success at 3 months postconversion was 70%. Karnofsky scores and liver function tests were significantly improved for patients continuing on therapy indicating clinical benefit in these patients. The safety profile of FK 506 is acceptable for such a high-risk group of patients. These preliminary clinical results support the conclusion that FK 506 can effectively control and reverse refractory rejection in a majority of liver transplantation patients.

Acute Disease↗
PubMed1993

Safety and efficacy of total thyroidectomy for differentiated thyroid carcinoma: a 20-year review.

Controversy continues to exist regarding the optimal extent of resection for differentiated thyroid carcinoma (DTC). Subtotal thyroidectomy has been advocated by some authors in expectation of lower complication rates, while others advocate total thyroidectomy to achieve better cure rates. To examine this issue, the medical records of 124 patients who underwent total thyroidectomy for DTC were retrospectively reviewed. Total thyroidectomy was the initial procedure in 115 patients, while nine patients had complete thyroidectomy following some type of subtotal resection. Concomitant procedures were performed in 47 patients. Ninety papillary, 20 mixed papillary-follicular variant, one Hürthle cell type, and 13 follicular carcinomas were performed. Tumors were bilateral or multicentric in 40 patients, with metastases present in one-third of patients at the same time of initial operation. Permanent hypoparathyroidism developed in two patients, and permanent ipsilateral recurrent laryngeal nerve palsy occurred in one patient, for an overall significant complication rate of 2.4 per cent. Tumor recurrence was noted at a mean of 19 months postoperatively in 14 patients. Ninety-six patients received adjuvant postoperative radioiodine therapy to ablate residual functioning thyroid tissue or suspected metastases. We conclude that total thyroidectomy as treatment for differentiated thyroid carcinoma carries a low rate of morbidity, treats occult contralateral disease, and should facilitate radioiodine scanning and ablation of residual functioning thyroid tissue or metastatic disease.

Adenocarcinoma↗
PubMed1992

The phage lambda gene Q transcription antiterminator binds DNA in the late gene promoter as it modifies RNA polymerase.

The bacteriophage lambda gene Q transcription antiterminator modifies RNA polymerase during an extended pause in elongation at nt +16 and +17 of the phage late gene promoter transcript. We show here that Q binds a specific DNA site between the -10 and -35 elements of the promoter as it interacts with the enzyme. We show that the pause must reflect a specialized elongation structure that is receptive to modification by Q, because Q does not bind to RNA polymerase stopped artificially after transcribing 16 nt of mutant DNA that does not encode the natural pause. Footprinting shows that RNA polymerase in the paused complex makes distinctive interactions with DNA in the region where Q binds; binding of Q, in turn, changes the footprint both at the Q-binding site and in the transcription bubble. Binding of Q to the paused transcription complex is stabilized by the transcription factor NusA, as expected from the dependence of lambda Q-mediated antitermination on NusA.

Bacteriophage lambda↗
PubMed1992

What are the contraindications for laparoscopic cholecystectomy?

Acute cholecystitis, morbid obesity, and previous upper abdominal surgery have been reported as relative contraindications to laparoscopic cholecystectomy. An analysis of 706 laparoscopic cholecystectomies performed at our institution was undertaken to determine if these relative contraindications led to increased morbidity, an increased rate of conversion to the open technique, or longer operating time. One hundred ninety-seven patients demonstrated one or more relative contraindications to laparoscopic cholecystectomy. Morbidity was not increased in patients with these risk factors, but conversion to open cholecystectomy was required in a greater percentage of patients with acute cholecystitis. We favor an attempt at laparoscopic cholecystectomy in patients with these risk factors; however, they should be counseled as to the increased risk of conversion to open cholecystectomy in the presence of acute cholecystitis.

Abdomen↗
PubMed1992

Evidence of genetic heterogeneity among the nondystrophic myotonias.

Recent in vitro electrophysiologic studies have demonstrated abnormal sodium channel gating in muscle from patients with Thomsen's disease and have called the chloride hypothesis into question. Abnormal sodium channel function, like myotonia, is a feature common to Thomsen's disease and several myotonias that are genetically linked to a chromosome-17q sodium channel locus. We present a pedigree segregating an allele for Thomsen's disease that is unlinked to this sodium channel locus, thus constituting evidence of genetic heterogeneity among the nondystrophic myotonias.

Child↗
PubMed1991

Rho-dependent transcription termination. Characterization of the requirement for cytidine in the nascent transcript.

By substituting template segments encoding AU-rich, GU-rich, and CA-rich transcripts for natural sequences upstream of the phage lambda rho-dependent tR1 termination site, we demonstrate that cytidines are required in the upstream RNA for rho-dependent termination to occur. These results are extended through in vitro mutagenesis of a template encoding an inactive AU-rich upstream sequence: certain mutant templates encoding new cytidines are able to activate rho-dependent termination. Cytidines must be dispersed over a region of the transcript in order for rho to be activated, although no specific pattern of cytidines appears to be required. The results show that no local clustering or regular spacing of cytidines is necessary and that cytidines are not used as a "ruler" to determine the location of termination sites. Rho is somewhat sensitive to the relative positions of cytidines since slightly different nascent transcripts activate rho termination activity to various degrees. A model is presented in which hexameric rho binds 78 nucleotides of contiguous RNA in a primary site, such that each monomer interacts with at least one cytidine somewhere in the 13 nucleotides allotted to the monomeric primary site.

Bacteriophage lambda↗
PubMed1991

Open versus laparoscopic cholecystectomy. A comparison of postoperative pulmonary function.

Upper abdominal surgery is associated with characteristic changes in pulmonary function which increase the risk of lower lobe atelectasis. Sixteen patients undergoing open cholecystectomy and 20 patients undergoing laparoscopic cholecystectomy were prospectively evaluated by pulmonary function tests (forced vital capacity [FVC], forced expiratory volume [FEV-1], and forced expiratory flow [FEF] 25% to 75%) before operation and on the morning after surgery to determine if the laparoscopic technique lessens the pulmonary risk. Fraction of the baseline pulmonary function was calculated by dividing the postoperative pulmonary function by the preoperative pulmonary function and multiplying by 100%. Postoperative FVC measured 52% of preoperative function for open cholecystectomy and 73% for laparoscopic cholecystectomy (p = 0.002). Postoperative FEV-1 measured 53% of baseline function for open cholecystectomy and 72% for laparoscopic cholecystectomy (p = 0.006). Postoperative FEF 25% to 75% measured 53% for open cholecystectomy and 81% for laparoscopic cholecystectomy (p = 0.07). It is concluded that laparoscopic cholecystectomy offers improved pulmonary function compared to the open technique.

Adult↗
PubMed1991

Characterization of the late-gene regulatory region of phage 21.

A segment of Escherichia coli bacteriophage 21 DNA encoding the late-gene regulator, Q21, and the late-gene leader RNA segment was sequenced; its structure is similar to those of the related phages lambda and 82. The leader RNA is about 45 nucleotides long and consists essentially entirely of sequences encoding the p-independent terminator that is the putative target of the antitermination activity of Q21. Like the corresponding regions of lambda and 82, the 21 late-gene promoter segment encodes an early transcription pause in vitro, at about nucleotide 18, during which Q21 presumably acts to modify RNA polymerase. The 21 Q gene, cloned in isolation, is active on the late-gene leader segment in trans, and its purified product is active as an antiterminator in vitro; Q21 represents a third late-gene antiterminator, in addition to those of lambda and 82. There is little evident similarity in the primary sequences of the three Q genes.

Amino Acid Sequence↗
PubMed1991

Paramyotonia congenita and hyperkalemic periodic paralysis map to the same sodium-channel gene locus.

Paramyotonia congenita (PC), an autosomal dominant muscle disease, shares some clinical and electrophysiological similarities with another myotonic muscle disorder, hyperkalemic periodic paralysis (HYPP). However, clinical and electrophysiologic differences allow differentiation of the two disorders. The HYPP locus was recently shown to be linked to a skeletal muscle sodium-channel gene probe. We now report that PC maps to the same locus (LOD score 4.4, theta = 0 at assumed penetrance of .95). These linkage results, coupled with physiological data demonstrating abnormal sodium-channel function in patients with PC, implicate a sodium-channel gene as an important candidate for the site of mutation responsible for PC. Furthermore, this is strong evidence for the hypothesis that PC and HYPP are allelic disorders.

DNA Probes↗
PubMed1990

Heterogeneous initiation due to slippage at the bacteriophage 82 late gene promoter in vitro.

RNAs synthesized in vitro by purified Escherichia coli RNA polymerase from a bacteriophage 82 promoter are heterogeneous at the 5' end. We show that this heterogeneity results from variable addition of extra adenine residues, allowed by slippage of the initial oligonucleotide pppAAA-OH against its DNA template sequence TTT. Slippage backward by one base allows another A to be added, giving pppAAAA-OH, and this cycle can continue more than 20 times before it is ended by incorporation of UMP encoded by the fourth template base A. Slippage is abolished by mutation of the TTT template sequence to TGT and is sensitive to the concentrations of UTP and ATP in the reaction mixture. Analysis of deletions, substitutions, and point mutants implies that the slippage reaction requires only the existence of TTT at the initiation site of the template strand, although changes in neighboring nucleotides slightly affect its efficiency.

Adenosine Triphosphate↗
PubMed1990

Nature of the SOS-inducing signal in Escherichia coli. The involvement of DNA replication.

The SOS genes of Escherichia coli, which include many DNA repair genes, are induced by DNA damage. Although the central biochemical event in induction, activation of RecA protein through binding of single-stranded DNA and ATP to promote cleavage of the LexA repressor, is known, the cellular event that provides this activation following DNA damage has not been well understood. We provide evidence here that the major pathway of induction after damage by a typical agent, ultraviolet light, requires an active replication fork; this result supports the model that DNA replication leaves gaps where elongation stops at damage-induced lesions, and thus provides the single-stranded DNA that activates RecA protein. In order to detect quantitatively the immediate product of the inducing signal, activated RecA protein, we have designed an assay to measure the rate of disappearance of intact LexA repressor. With this assay, we have studied the early phase of the induction process. LexA cleavage is detectable within minutes after DNA damage and occurs in the absence of protein synthesis. By following the reaccumulation of LexA in the cell, we detect repair of DNA and the disappearance of the inducing signal. Using this assay, we have measured the LexA content of wild-type and various mutant cells, characterized the kinetics and conditions for development of the inducing signal after various inducing treatments and, finally, have shown the requirement for DNA replication in SOS induction by ultraviolet light.

Bacterial Proteins↗
PubMed1990

Naloxone in septic shock.

Treatment of septic shock is a persistent dilemma. The clinical use of agents such as naloxone has resulted in variable success. Because the dosage and timing of these agents are considered critical factors in their efficacy, we investigated both dosage and timing of naloxone. Thirteen consecutive patients with documented septic shock and resistance to a one-liter fluid challenge underwent invasive hemodynamic monitoring and the administration of naloxone by initial bolus of 0.03 mg/kg followed by infusion at a rate of 0.2 mg/kg.h over one hour. During the one-hour observation period, iv fluid administration, concomitant pressor agents, and respirator values were constant. After infusion, adjustments in fluid administration, respirator status, and pressor agents were made as required by the clinical situation. A significant increase in mean arterial pressure (MAP) over baseline (60 +/- 3 mm Hg) was noted at 5 min (77 +/- 6 mm Hg, p less than .005) and at 30 min (73 +/- 6 mm Hg, p less than .025). Similarly, a significant increase in systolic arterial pressure was noted over prenaloxone levels (89 +/- 3 mm Hg) at 5 min (114 +/- 6 mm Hg, p less than .001), 30 min (107 +/- 8 mm Hg, p less than .05), and at one hour (106 +/- 8 mm Hg, p less than .05). There was a moderate nonsignificant increase in cardiac index, pulmonary capillary wedge pressure, and systemic vascular resistance. No side-effects to naloxone were noted in our group. No effect on survival could be demonstrated. We found no overall effect on mortality. However, by its increase of MAP, naloxone may serve as a temporizing agent during the treatment of critically ill patients with septic shock.

Adult↗