PubMed HealthSearch

Biomedical subjects

R J Rubin

Publications and source records attributed to R J Rubin.

At least 19 recordsLinked to original sources

Arterial thromboembolic complications of inflammatory bowel disease. Report of three cases.

Extraintestinal manifestations of inflammatory bowel disease are legion and are demonstrated in one-third of those afflicted. In general, they do not mandate surgery. Three patients with active pancolonic ulcerative colitis developed arterial thromboembolic complications prior to surgical treatment. Thromboembolic complications are not fully understood, as is evidenced by the paucity of information in the literature, and only sporadic cases of arterial thromboemboli are found. These have been described primarily in the postsurgical patient. To ascertain whether others have encountered similar cases, a survey form was distributed to members of The American Society of Colon and Rectal Surgeons, yielding an additional 54 patients with thromboembolic complications. Approximately two-thirds were deep venous thromboses and/or pulmonary emboli. Ten patients had cerebrovascular accidents, and eight had arterial emboli. Eleven patients, over 21 percent, suffered multiple events. There were four resultant mortalities. An arterial thromboembolic event in a patient with ulcerative colitis is usually associated with pancolonic disease, has a poor long-term prognosis, and is an indication for colectomy.

Adult

Computed tomography in the initial management of acute left-sided diverticulitis.

Computed tomography (CT) was used in place of contrast enemas as the initial imaging study to evaluate patients with the clinical diagnosis of acute sigmoid diverticulitis. This report attempts to clarify the role of CT in the management of acute sigmoid diverticulitis by reviewing its usefulness in the diagnosis and treatment of 59 patients. CT established that three patients (5 percent) were hospitalized with an incorrect clinical diagnosis. Thirty-seven patients (62.7 percent) were identified as having uncomplicated acute diverticulitis. These patients were all treated successfully with nonsurgical therapies and were discharged in an average of 6.8 days. In the remaining 19 patients (32.2 percent), CT revealed complicated acute diverticulitis by identifying abscess, fistula, peritonitis, or obstruction. Eleven of these 19 patients required urgent surgery or CT-guided percutaneous drainage of an abscess. The four patients whose abscesses were drained percutaneously responded favorably and underwent an elective single-stage resection. The average hospital stay for patients with complicated diverticulitis was 13.6 days. Computed tomography is a useful aid in the initial management of patients with acute diverticulitis. It is a noninvasive test that recognizes and stratifies patients according to the severity of their disease. It has the further advantage of providing information about extracolonic pathology and anatomic variation useful for surgical planning. Additionally, early CT-guided needle drainage allowed downstaging of complicated diverticulitis, avoided emergent surgery, and permitted single-stage elective surgical resection.

Abscess

Anterior perineal sinus.

Each year we treat several patients with an anterior perineal sinus tract. They do not conform to commonly encountered perineal problems such as pilonidal disease, epidermal cysts, hidradenitis, fistulous abscess, or inflammatory bowel disease. In an effort to improve understanding of the problem and its clinical significance, we reviewed our practice records for the period from 1968 through 1988. Fifty-six patients underwent surgery for an anterior perineal sinus tract. In 31 patients, the clinical and pathologic condition defied classical diagnostic categorization. We have termed these lesions "anterior perineal sinuses." Their clinical characteristics, treatment, and pathologic assessment from the body of this report. Male predominance (87 percent) and midlife presentation (average age, 44 years) characterized this group. Local symptoms were present from several weeks to several years prior to treatment. Local anesthesia (74 percent) and limited surgery (100 percent) resulted in complete healing in all patients (average, 7 weeks). A 15 percent recurrence rate was noted. The pathologic evaluation demonstrated acute and chronic dermal and subcutaneous inflammation. The etiology of this process remains uncertain. Its predominance along the median raphe suggests a congenital midline inclusion disorder.

Adult

Mutagenicity and metabolism of dimethyl phthalate and its binding to epidermal and hepatic macromolecules.

As an active ingredient in insect repellents, dimethyl phthalate (DMP) had previously been shown to produce chromosomal aberrations in the livers of rats following subchronic application of the phthalate to skin. When we tested DMP in the Ames mutagenesis assay, it produced in bacterial tester strain TA100 (but not TA98) a dose-related mutagenic response that was abolished by NAD- and NADP-independent metabolism associated with rat liver microsomal preparations (S9). In a host-mediated mutagenesis assay, rats were injected ip with DMP (2 g/kg body weight); urine was collected for 24 h, extracted, and analyzed for mutagenic activity and phthalic acid-containing derivatives. The extracted urine was not mutagenic to TA100 and contained an equivalent of 1.96 mg phthalate/ml urine. More than 97% of the phthalic acid-containing derivatives present in the extracted urine consisted of the nonmutagenic metabolite of DMP, monomethyl phthalate (MMP). In vitro experiments showed that rat liver homogenates hydrolyzed 93% of carbonyl-labeled 14C-DMP (7.7 mM) to MMP in 2 h and bound 0.07 nmol of [14C]phthalate/mg liver macromolecules. By contrast, rat epidermal homogenates metabolized only 5% and bound 38-fold higher levels of carbonyl-labeled 14C-DMP (2.66 nmol/mg of macromolecules), with no detectable binding to nucleic acids. Compared to epidermis and plasma, liver had a fivefold higher rate of DMP monoesterase activity (1240 nmol/h/mg protein), which, when inhibited by 67%, resulted in a 4.4-fold increase in phthalate-bound hepatic macromolecules (0.31 vs. 0.07 nmol of carbonyl-labeled 14C-DMP/mg macromolecules). In addition to MMP, formaldehyde was produced during the metabolism of DMP by liver. When ethanol was used to inhibit the oxidation of DMP-derived methanol by hepatic homogenates, there resulted a 74% reduction in the accumulation of formaldehyde and similar reductions of 71 and 73% in the binding of methyl-labeled 14C-DMP to nucleic acids and macromolecules. (Methyl-labeled, unlike carbonyl-labeled, 14C-DMP yields a 14C-labeled methanol when hydrolyzed.) These results indicate that the DMP diester is a weak bacterial mutagen, which binds to epidermal and hepatic macromolecules other than nucleic acids, and that although the rapid hepatic metabolism of DMP to its monoester (MMP) and methanol affords protection against higher levels of phthalate binding as well as against DMP-induced bacterial mutagenesis, it also oxidizes DMP-derived methanol to formaldehyde, a metabolite that binds macromolecules, including nucleic acids.

Animals

Seton management of complex anorectal fistulas in patients with Crohn's disease.

Anorectal fistulas associated with Crohn's disease are difficult to manage, particularly when the rectum is diseased. Significant morbidity has been associated with both medical and surgical therapy. Although conventional therapy is acceptable in the management of simple fistulas in Crohn's disease, these approaches often exacerbate rather than ameliorate problems in patients with complex fistulas. The authors report ten cases of complex fistulas in patients with Crohn's disease managed with their technique of long-term, indwelling setons. These setons are placed through the fistula tract and tied loosely to maintain the patency of the fistula without cutting through the sphincters. At the time of insertion, although abscesses are incised and drained, no attempt is made to divide the superficial tissues or sphincter overlying the fistulous tract. The patients ranged in age from 23 to 81 years and had a history of Crohn's disease for 1 to 20 years. All cases resulted in excellent palliation. No patient required a proximal colostomy. These patient have been followed for four months to seven years. Despite severe proctitis in six of these patients at the initial operation, no patient has required a proctectomy. The authors believe this technique achieves adequate palliation and should be employed as the procedure of choice in patients with complex anal fistulas associated with Crohn's disease.

Adult

Diffusion and redistribution of lipid-like molecules between membranes in virus-cell and cell-cell fusion systems.

The kinetics of redistribution of lipid-like molecules between the membranes of two fused spherical vesicles is studied by solving the time-dependent diffusion equation of the system. The effects on the probe redistribution rate of pore size at the fusion junction and the relative sizes of the vesicles are examined. It is found that the redistribution rate constant decreases significantly, but not drastically, as the relative size of the pore to that of the vesicles decreases (the bottleneck effect). In general, the time scale of the probe redistribution rate is determined by the size of the vesicles that is loaded with the probe before the activation of the fusion. For a pore size 50 A in diameter and a typical diffusion coefficient of 10(-8) cm2/s for lipids, the mixing half times for typical virus-cell and cell-cell fusion systems are less than 30 ms and above 200 s, respectively. Thus, although the redistribution of lipid-like probes by diffusion is not rate limiting in virus-cell fusion, redistribution by diffusion is close to rate limiting in spike-protein mediated cell-cell fusion.

Biophysical Phenomena

Complications of colostomies.

One hundred twenty-six patients underwent 130 end colostomies, 44 for benign and 86 for malignant disease, and were followed for an average of 35 months. The left or sigmoid colon was used in 99 and the transverse colon in 31. Stomas were made electively in 98 patients and urgently in 32. Seventy-six stomas were brought out through the incision and 54 from separate sites. There were 69 complications in 55 patients (44 percent) including 11 strictures, 9 wound infections, 14 hernias, 9 small-bowel obstructions, 4 prolapses, 2 abscesses, 1 peristomal fistula, 17 skin erosions, and 2 poor stoma locations. Fifteen complications required reoperation. Five of these procedures included stoma revision. Total numbers of complications were not related to the stoma site, the disease process, the urgency of the procedure, or the segment of colon used. Wound infections, however, were increased in urgently made stomas. The incidence of hernia was equivalent in stomas brought out through the incision or at a separate site. Forty-one patients (30 percent) had 43 colostomies closed an average of 3.5 months after creation. Thirteen patients had 14 complications--5 wound infections, 6 hernias, 2 small-bowel obstructions, and 1 rectovaginal fistula. One patient died. Four patients required reoperation. There were no anastomotic leaks. Complications were equivalent in Hartmann closures and transverse colostomy closures. Complications were similar in stomas created for cancer and those created for diverticular disease.

Colonic Diseases

The possible role of the ethanol-inducible isozyme of cytochrome P450 in the metabolism and distribution of carbon disulfide.

Acute treatment with ethanol and other alcohols has been shown to potentiate the hepatotoxicity of certain xenobiotics, in part via induction of the mixed-function oxidase (MFO) system. Carbon disulfide (CS2)-induced hepatotoxicity and inhibition of the MFO system have been shown to be a consequence of MFO metabolism. In the present study, the ability of several different alcohols to induce the hepatic MFO metabolism of CS2 and the effects of this induction on CS2 distribution and hepatotoxicity were examined in rats. Eighteen hours after alcohol administration (1/2 LD50 dose, po), CS2 microsomal MFO metabolism was significantly enhanced, in order of descending potency, by isopropanol, methanol, and ethanol pretreatments, but not by isobutanol pretreatment. The degree of enhancement of CS2 metabolism by different alcohols paralleled the enhancement of nitroanisole O-demethylation and aniline hydroxylation, MFO activities associated with the ethanol-inducible isozyme of cytochrome P450. CS2 (1 mg/kg, ip, 3 hr) inhibited only the cytochrome P450-mediated activities enhanced by alcohol pretreatment. These results suggest that CS2 metabolism is catalyzed by the ethanol-inducible isozyme. Alcohol-induced rats had significantly more 14CS2-derived radioactivity in the liver than control and isobutanol-pretreated rats 3 hr after dosing (1 mg/kg, ip). However, only methanol pretreatment resulted in an increased retention of 14CS2-derived radioactivity in plasma, brain, and kidney. Unlike other alcohol pretreatments, methanol decreased the total 14C expired during the 3-hr period after CS2 dosing and caused a significant (twofold) increase in plasma glutamic-pyruvic transaminase, measured 24 hr after CS2 exposure (625 mg/kg). These data indicate that alcohol induction of MFO-dependent CS2 metabolism per se is not sufficient to result in CS2-induced hepatic damage although it does lead to loss of specific cytochrome P450 function.

Alanine Transaminase

Mean lifetime of microtubules attached to nucleating sites.

A simple two-phase (cap; no cap) macroscopic model describing the kinetic behavior at a labile tip of a microtubule has been proposed [Hill, T. L. (1984) Proc. Natl. Acad. Sci. USA 81, 6728-6732]. In the model, a microtubule exists either in a slowly growing phase (first-order rate constant, alpha) characterized by the existence of a GTP-tubulin cap at the growing tip; or the same microtubule exists in a rapidly shrinking phase (first-order rate constant, beta), which is entered if/when the GTP-tubulin cap is lost through a fluctuation, thus exposing GDP-tubulin subunits, which constitute the body of the microtubule. Transition between the two phases--i.e., loss of a cap (first-order rate constant, k) or formation of a new cap (first-order rate constant, k') occurs very infrequently and in a stochastic manner. In vitro experiments with centrosome-nucleated microtubules by Mitchison and Kirschner and Monte Carlo kinetic simulations, based on a realistic set of microscopic rate constants that apply to the end of a microtubule, suggest this alternation between two "quasimacroscopic" phases. In this paper, I outline the calculation of the mean lifetime of a microtubule nucleated on a centrosome by using Hill's model. For a microtubule M units long in the slowly growing phase, the mean lifetime for complete depolymerization is [M(k + k') + alpha + beta](beta k - alpha k')-1, provided that beta k greater than alpha k'. If the microtubule is in the rapidly shrinking phase, then the mean lifetime is M(k + k')(beta k - alpha k')-1, provided that beta k greater than alpha k'. In case beta k less than alpha k', the microtubule grows indefinitely, and the mean lifetime is infinite.

Adenine Nucleotides

Electrocoagulation of selected carcinoma of the rectum.

Abdominoperineal resection for the treatment of carcinoma of the rectum has been the benchmark for all other forms of therapy since Miles described the procedure in 1908. During the past 25 years, 81 patients have had carcinoma of the rectum treated curatively by electrocoagulation and have been observed for five years or more. Treatment was selectively applied to those patients whose tumors were less than 7.5 centimeters from the anal verge with less than 50 per cent of the rectum involved. All of the tumors were freely movable. The over-all five year survival rate was 47 per cent. Thirty-one of the 81 patients underwent conversion to abdominoperineal resection because of recurrence. The survival rate for those treated by electrocoagulation alone was 58 per cent and for those converted to abdominoperineal resection, 29 per cent. The survival rate was 65 per cent for those with lesions less than 4 centimeters in diameter versus 30 per cent for those with lesions more than 4 centimeters. The morbidity rate was 21.0 per cent and the mortality rate was 2.7 per cent. There were an additional 33 patients treated for palliation with only one five year survivor. Electrocoagulation for the treatment of carcinoma of the distal part of the rectum is a reasonable alterative to abdominoperineal resection when selectively applied.

Adenocarcinoma