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Biomedical subjects

A J Stein

Publications and source records attributed to A J Stein.

17 recordsLinked to original sources

Structural studies of MIP synthase.

The conversion of glucose 6-phosphate to 1-L-myo-inositol 1--phosphate (MIP) by 1-L-myo-inositol 1-phosphate synthase (MIP synthase) is the first committed and rate-limiting step in the de novo biosynthesis of inositol in all eukaryotes. The importance of inositol-containing molecules both as membrane components and as critical second messenger signal-transduction species make the function and regulation of this enzyme important for a host of biologically important cellular functions including proliferation, neurostimulation, secretion and contraction. MIP synthase has been overexpressed in Esherichia coli and purified to homogeneity by chromatographic methods. Two crystal forms of MIP synthase were obtained by the hanging-drop vapor-diffusion method. Native data sets for both crystal forms were collected in-house on a Rigaku R-AXIS IIC imaging-plate detector. Crystal form I belongs to space group C2, with unit-cell parameters a = 153.0, b = 96.6, c = 122.6 A, beta = 126.4 degrees, and diffracts to 2.5 A resolution. Crystal form II belongs to space group P2(1), with unit-cell parameters a = 94.5, b = 186.2, c = 86.5 A, beta = 110.5 degrees, and diffracts to 2.9 A resolution.

Crystallization↗

Patellofemoral resurfacing at total knee arthroplasty.

A retrospective review of 268 primary total knee arthroplasties (TKAs) with a mean follow-up of four years is presented. The patellae were resurfaced in all cases. There were six complications (2.2%) referable to the patellofemoral articulation: three subluxations, one patellar fracture, one loosening of a metal-backed patellar component, and one patellar tendon avulsion. Successful patellofemoral resurfacing (PFR) can be accomplished with minimal complications if the following technical considerations are met: 5-7 degrees of valgus alignment; medial placement of the patellar component; taking care not to increase either the AP diameter of the knee or the thickness of the patella; avoiding internal rotation of either the tibial or femoral components and proper soft tissue balancing. A thorough review of patellofemoral complications after TKA is presented, and technical considerations relevant to the successful performance of PFR are discussed.

Adult↗

Heterotopic ossification following primary total knee arthroplasty.

Heterotopic ossification is a rare complication following primary total knee arthroplasty and may be symptomatic if massive enough. The authors retrospectively reviewed 158 primary total knee arthroplasties from 1985 to 1989 and found 6 cases (3.8%) of heterotopic ossification. Patients were graded before and after surgery according to the Hospital for Special Surgery total knee arthroplasty score and their histories were reviewed for the presence of recognized risk factors for heterotopic ossification and whether a manipulation under anesthesia was performed. This report describes the incidence of, appearance of, and clinical risk factors for heterotopic ossification following primary total knee arthroplasty in this series. A radiographic grading system is proposed.

Aged↗

Protective role of intestinal flora against infection with Pseudomonas aeruginosa in mice: influence of antibiotics on colonization resistance.

Swiss white mice were given ampicillin, clindamycin, kanamycin, metronidazole, or streptomycin in drinking water for a period of 3 weeks. One week after the initiation of antibiotic administration, the treated mice and untreated control mice were challenged orally with approximately 10(8) viable, streptomycin-resistant (SR) Pseudomonas aeruginosa isolates. All five of the antibiotics decreased the resistance of the mice to intestinal colonization with SR P. aeruginosa, as reflected by an increased fecal carriage of the organism and an increase in population levels of SR P. aeruginosa in feces as compared with untreated controls. Metronidazole was least effective in this regard. The antibiotics lowered the dose of SR P. aeruginosa that resulted in implantation in 50% of the mice ID50 to various degrees. Administration of streptomycin, the most effective antibiotic, caused a 10,000-fold decrease in ID50 as compared with untreated controls. Oral inoculation of approximately 10(8) organisms of SR P. aeruginosa resulted in translocation of the organism to the mesenteric lymph nodes, spleens, or livers of 13 or 17 streptomycin-treated mice, 1 of 20 clindamycin-treated mice, and 1 of 14 metronidazole-treated mice. Translocation was not observed, however, in ampicillin- or kanamycin-treated animals. Antibiotic activity was detected in the cecal contents of streptomycin-, kanamycin, and clindamycin-treated mice but not in the cecal contents of ampicillin- or metronidazole-treated animals.

Ampicillin↗

Corynanthine and aqueous humor dynamics in rabbits and monkeys.

The effects of corynanthine tartrate, a selective alpha 1-adrenergic receptor antagonist, were studied on intraocular pressure by pneumatonometry, outflow facility by tonography, and aqueous humor flow by fluorophotometry in laboratory animals. Unilateral topical administration of 5% corynanthine significantly lowered mean IOP (+/- SEM) in rabbits for at least six hours, in ten awake monkeys for six hours, and in ten monkeys anesthetized with ketamine for four hours. The maximum effect in awake monkeys occurred two hours after drug administration, from 15.8 +/- 0.5 mm Hg to 12.7 +/- 0.5 mm Hg, with no substantial change in control eyes. No change in outflow facility was demonstrated in 11 monkeys two hours after 5% corynanthine administration. Aqueous humor flow rates did not change in 12 monkeys up to three hours after drug administration. Corynanthine may act by increasing uveoscleral outflow.

Adrenergic alpha-Antagonists↗

Staging errors in clinically localized prostatic cancer.

The interrelationships among tumor grade, local tumor extension, lymph node involvement and early treatment failure were examined in 96 consecutive patients with clinical stage A (11 patients) or B (85 patients) prostatic cancer who were considered potential candidates for radical prostatectomy. In this series 20 of the 82 patients (24 per cent) who underwent radical prostatectomy had local tumor extension beyond the prostatic capsule and 27 of the 88 patients (31 per cent) who had lymph node dissections had nodal involvement. Of the entire group of 96 patients 38 (40 per cent) had either local extension and/or nodal involvement. A direct correlation was observed between clinical stage and the incidence of local tumor extension but not between clinical stage and nodal involvement. However, there was a striking correlation between surgical stage and lymph node involvement in patients who underwent radical prostatectomy. A direct correlation also was observed between tumor grade, and local extension and nodal involvement. Analysis of multiple parameters revealed that clinical grade of tumor considered together were more predictive of nodal involvement than either parameter alone. Early treatment failures occurred in 5 patients, all of whom were understaged clinically.

Follow-Up Studies↗

Accuracy of frozen section detection of lymph node metastases in prostatic carcinoma.

To examine the accuracy of frozen sections in the detection of pelvic lymph node metastases in patients with prostatic cancer, the results of frozen and paraffin sections were compared in 75 consecutive patients with clinical stage A or B prostatic cancer. Frozen sections were positive for cancer in 16 patients (21 per cent), 14 of whom had gross lymphadenopathy, and in all cases cancer was confirmed on paraffin sections. Of 59 patients with negative frozen sections 11 (19 per cent) had paraffin sections positive for cancer. However, in 10 of these 11 patients there were only 1 or 2 microscopic metastases. Thirteen other patients with normal-appearing lymph nodes did not have frozen sections obtained at the time of operation and metastases were not found on paraffin sections. There was a direct correlation between tumor grade and nodal involvement. The results suggest that frozen sections are of limited reliability in identifying lymph node metastases in patients who do not have gross lymphadenopathy. The extent to which this inaccuracy may result in the selection of inappropriate therapy remains to be determined.

Frozen Sections↗

Grading errors in prostatic needle biopsies: relation to the accuracy of tumor grade in predicting pelvic lymph node metastases.

To examine how accurately needle biopsies reflect the true histologic grade of prostatic cancers the histologic grade of needle biopsy specimens was compared to that of the radical prostatectomy specimen in 66 consecutive patients. Needle biopsies were given a lower grade than the prostatectomy specimen in 21 patients (33 per cent) and a higher grade in 5 patients (8 per cent). To examine how accurately the tumor grade of needle biopsy specimens predicts lymph node metastases in patients with clinical stage B prostatic cancer the needle biopsy grade was compared to lymph node metastases in 78 consecutive patients who underwent staging pelvic lymphadenectomy. Thirteen per cent of the patients with well differentiated cancer, 50 per cent with moderately differentiated cancer and 64 per cent with poorly differentiated cancer had pelvic lymph node metastases. In most cases grading errors did not influence the capacity of needle biopsies to predict nodal involvement. We conclude that although prostatic needle biopsies are associated with significant errors in grading they do provide valuable information about the predominant histologic pattern, which reflects the biologic potential of the tumor.

Biopsy, Needle↗

Surgical treatment of pulmonary hydatidosis.

Thirteen years' experience with the surgical treatment of hydatid cystic disease of the lung is analyzed. An unselected series of 149 consecutive patients is reviewed. The preoperative diagnosis was exact in 98% of the cases, our conclusions being based primarily upon radiologic findings. The procedures used were puncture-aspiration with the trocar-suction cup in 139 cases, enucleation in four, wedge resection in two, segmentectomy in one, and lobectomy in three. In 19 cases, capitonnage of the residual cavity was performed: in the rest, partial resection of the pericystic membrane was performed, everting the cavity toward the pleura and using a high negative pressure vacuum through the thoracic drainage tubes. The early mortality was 1%. The persistence of a residual cavity was five times more frequent in those cases in which capitonnage was performed. The recurrence rate of the disease after an average follow-up of 37.5 months per patient was 0% in patients with an unruptured cyst and 9.3% in those in whom the cyst had ruptured prior to operation. As a whole, the percentage of morbidity and mortality in the short and long terms in this series is superior to those quoted in the literature, where other procedures were used.

Adolescent↗

Adenomatous polyps of the prostatic urethra: a cause of hematospermia.

Hematospermia is a common urologic problem that is not always evaluated by cystoscopic examination. We report on 4 patients with hematospermia in whom polypoid lesions were observed in the prostatic urethra near the verumontanum on cystoscopic examination. In 3 of these patients the lesions were adenomatous polyps, resembling a normal prostate, and in 2 the hematospermia resolved following resection. In the remaining patient the lesion proved to be an intraductal carcinoma. We believe that cystoscopy is indicated in all patients with hematospermia that does not resolve on antibiotic therapy. Polypoid lesions in the prostatic urethra should be resected as diagnostic and sometimes therapeutic measure.

Hemorrhage↗

Efficacy of nelfinavir in patients switched from ritonavir/saquinavir combination antiretroviral therapy.

UNLABELLED: Based on available data and expert opinion, the IAS-USA treatment guidelines recommend "selective substitution" of the medication thought most likely to be causing a side effect for one that should have a different side effect profile. PURPOSE: This study evaluates the short-term virological efficacy of selective substitution with nelfinavir-nucleoside combination therapy in individuals with plasma viral RNA below 400 copies/mL. METHOD: This study involved a retrospective chart review at five large urban HIV Clinical practice settings and included 19 patients taking combination therapy including ritonavir with saquinavir. We performed selective substitution with a nelfinavir combination. Our main outcome measure was plasma HIV-1 RNA (Amplicor) obtained during the period between weeks 12 to 18. RESULTS: We identified 19 HIV-1-infected individuals with evidence of viral suppression as defined by a viral load below 400 copies/mL while taking dual nucleoside reverse transcriptase inhibitors with ritonavir/saquinavir. Reasons for switching included adverse effects (37%) or preference for nelfinavir due to the possibility of a better defined salvage regimen (63%). We defined a composite viral endpoint indicative of continued viral suppression using the first 12 to 18 weeks following the medication change. We found that 73% maintained undetectable viral loads (plasma HIV RNA below 400 copies/mL) during this period. CONCLUSION: These data suggest that any medication adjustment should be made cautiously, as there may be some potential risk in a substitution. Selective substitution of a medication that has undesirable side effects or other characteristics should be considered when the possible risks of the loss of viral suppression are outweighed by the potential benefits of that substitution.

Anti-HIV Agents↗