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Biomedical subjects

M Gross

Publications and source records attributed to M Gross.

At least 217 records · Page 12Linked to original sources
PubMed1998

Rizatriptan (MAXALT) for the acute treatment of migraine and migraine recurrence. A placebo-controlled, outpatient study. Rizatriptan 022 Study Group.

Rizatriptan is a novel 5-HT1B/1D agonist which is rapidly absorbed after oral administration. The efficacy and tolerability of oral rizatriptan (5 mg and 10 mg) were examined in this multicenter, double-blind, outpatient study of 1473 migraineurs which featured randomized, placebo-controlled treatment of migraine recurrences. On experiencing moderate or severe migraine headaches, patients rated headache severity prior to dosing and at 30-minute intervals for 2 hours after dosing. Onset of effect was seen as early as 30 minutes after dosing with rizatriptan 10 mg. At 2 hours postdose, the percentage of patients with pain relief was significantly higher after rizatriptan 5 mg (62%) or 10 mg (71%) compared with placebo (35%). Complete relief was also significantly higher after rizatriptan 5 mg (33%) and 10 mg (42%) compared with placebo (10%). In patients experiencing headache recurrence after initial benefit, further relief was obtained in 71% with rizatriptan 5 mg (placebo 54%) and in 82% with rizatriptan 10 mg (placebo 44%). Complete relief of recurrent headache was obtained in 36% with rizatriptan 5 mg, 49% with rizatriptan 10 mg, and 15% with placebo (P < 0.05). The most common drug-related adverse experiences were dizziness, somnolence, asthenia/fatigue, and nausea (the incidences of which were low and dose related). There was no increase in the incidence of adverse experiences after use of up to three doses of rizatriptan within 24 hours. We conclude that both doses of rizatriptan are effective and well tolerated in the acute treatment of migraine and migraine recurrence, with the 10-mg dose preferred as it is more effective with a faster onset of action.

Acute Disease↗
PubMed1998

[Interactive computer-assisted learning program for diagnosis and therapy of recurrent laryngeal nerve paralysis].

BACKGROUND: With the increasing capacity of personal computers more and more multimedia training programs are becoming available which make use of these possibilities. Computer-based presentation is usually interesting because it is visually attractive. However, the extent to which computer-based training programs correspond to international standards of quality of software ergonomics has never been the subject of systematic research. Another question is how much these programs motivate learning and what increase in knowledge can be achieved by using them. METHODS AND RESULTS: Using a multimedia interactive training program developed in our facility, 100 medical students were asked to evaluate the program after they had been using it for about one hour. In a questionnaire they first rated suitability for the task, self-descriptiveness, controllability, conformity with user expectation, error tolerance, suitability for individualization, and suitability for learning on a bipolar scale from "---" to "+3" (in numbers 1, worst result, to 7, best result). The median values achieved were rated between 6.0 and 6.2--software ergonomic criteria of the program ranged from good to very good. The second part was a subjective evaluation of the program's ability to deliver "medical knowledge which is relevant for the exam" (median = 6.0), "knowledge about systematic procedure in medicine" (median = 5.5), "knowledge about sensible use of diagnostic methods" (median = 6.0), "knowledge about clinical methods", and "experience with selective learning" (median = 6.0). This part was also rated good to very good. The third part of the questionnaire involved a pretest-posttest comparison. Two groups of students were asked how much benefit they had achieved by using the program. It was shown that the students were able to answer the exam questions significantly better than the control questions after they had used the program. CONCLUSION: This study confirms that the interactive computer-based training program is very well suited for providing knowledge in on appealing manner in an instructional setting.

Adult↗
PubMed1998

Rectal microbicides for U.S. gay men. Are clinical trials needed? Are they feasible? HIVNET Vaccine Preparedness Study Protocol Team.

BACKGROUND AND OBJECTIVES: Incomplete condom use during anal sex persists among gay men; microbicides may provide additional protection. Despite the absence of efficacy or safety data, many gay men use sexual lubricants containing nonoxynol-9 (N-9), a detergent-based spermicide under evaluation for efficacy as a vaginal microbicide. GOAL: Evaluate unprotected sex, lubricant use, and attitudes regarding possible participation in clinical trials of rectal microbicides among high-risk human immunodeficiency virus-(HIV) seronegative U.S. gay men in six cities. STUDY DESIGN: A total of 3,257 gay men were interviewed and responded to a self-administered questionnaire at enrollment into a longitudinal cohort study of HIV seroincidence. RESULTS: Among 2,216 men who practiced receptive anal intercourse in the previous 6 months, 438 (20%) reported they never used condoms. More than three fourths of 3,093 men who had anal sex used lubricants more than 80% of the time. 41% of whom actively sought N-9 containing products. About two thirds said they were definitely or probably willing to participate in rectal microbicide clinical trials. CONCLUSION: Condom use is imperfect among men who report anal sex. N-9 lubricants are popular. Most gay men in this cohort indicate willingness to participate in rectal microbicide studies.

Adolescent↗
PubMed1998

The herpes simplex virus US11 protein effectively compensates for the gamma1(34.5) gene if present before activation of protein kinase R by precluding its phosphorylation and that of the alpha subunit of eukaryotic translation initiation factor 2.

In herpes simplex virus-infected cells, viral gamma134.5 protein blocks the shutoff of protein synthesis by activated protein kinase R (PKR) by directing the protein phosphatase 1alpha to dephosphorylate the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2alpha). The amino acid sequence of the gamma134.5 protein which interacts with the phosphatase has high homology to a domain of the eukaryotic protein GADD34. A class of compensatory mutants characterized by a deletion which results in the juxtaposition of the alpha47 promoter next to US11, a gamma2 (late) gene in wild-type virus-infected cells, has been described. In cells infected with these mutants, protein synthesis continues even in the absence of the gamma134.5 gene. In these cells, PKR is activated but eIF-2alpha is not phosphorylated, and the phosphatase is not redirected to dephosphorylate eIF-2alpha. We report the following: (i) in cells infected with these mutants, US11 protein was made early in infection; (ii) US11 protein bound PKR and was phosphorylated; (iii) in in vitro assays, US11 blocked the phosphorylation of eIF-2alpha by PKR activated by poly(I-C); and (iv) US11 was more effective if present in the reaction mixture during the activation of PKR than if added after PKR had been activated by poly(I-C). We conclude the following: (i) in cells infected with the compensatory mutants, US11 made early in infection binds to PKR and precludes the phosphorylation of eIF-2alpha, whereas US11 driven by its natural promoter and expressed late in infection is ineffective; and (ii) activation of PKR by double-stranded RNA is a common impediment countered by most viruses by different mechanisms. The gamma134.5 gene is not highly conserved among herpesviruses. A likely scenario is that acquisition by a progenitor of herpes simplex virus of a portion of the cellular GADD34 gene resulted in a more potent and reliable means of curbing the effects of activated PKR. US11 was retained as a gamma2 gene because, like many viral proteins, it has multiple functions.

Animals↗
PubMed1998

The second-site mutation in the herpes simplex virus recombinants lacking the gamma134.5 genes precludes shutoff of protein synthesis by blocking the phosphorylation of eIF-2alpha.

In cells infected with the herpes simplex virus 1 (HSV-1) recombinant R3616 lacking both copies of the gamma134.5 gene, the double-stranded protein kinase R (PKR) is activated, eIF-2alpha is phosphorylated, and protein synthesis is shut off. Although PKR is also activated in cells infected with the wild-type virus, the product of the gamma134.5 gene, infected-cell protein 34.5 (ICP34.5), binds protein phosphatase 1alpha and redirects it to dephosphorylate eIF-2alpha, thus enabling sustained protein synthesis. Serial passage in human cells of a mutant lacking the gamma134.5 gene yields second-site, compensatory mutants lacking various domains of the alpha47 gene situated next to the US11 gene (I. Mohr and Y. Gluzman, EMBO J. 15:4759-4766, 1996). We report the construction of two recombinant viruses: R5103, lacking the gamma134. 5, US8, -9, -10, and -11, and alpha47 (US12) genes; and R5104, derived from R5103 and carrying a chimeric DNA fragment containing the US10 gene and the promoter of the alpha47 gene fused to the coding domain of the US11 gene. R5104 exhibited a protein synthesis profile similar to that of wild-type virus, whereas protein synthesis was shut off in cells infected with R5103 virus. Studies on the wild-type parent and mutant viruses showed the following: (i) PKR was activated in cells infected with parent or mutant virus but not in mock-infected cells, consistent with earlier studies; (ii) lysates of R3616, R5103, and R5104 virus-infected cells lacked the phosphatase activity specific for eIF-2alpha characteristic of wild-type virus-infected cells; and (iii) lysates of R3616 and R5103, which lacked the second-site compensatory mutation, contained an activity which phosphorylated eIF-2alpha in vitro, whereas lysates of mock-infected cells or cells infected with HSV-1(F) or R5104 did not phosphorylate eIF-2alpha. We conclude that in contrast to wild-type virus-infected cells, which preclude the shutoff of protein synthesis by causing rapid dephosphorylation of eIF-2alpha, in cells infected with gamma134.5(-) virus carrying the compensatory mutation, eIF-2alpha is not phosphorylated. The activity made apparent by the second-site mutation may represent a more ancient mechanism evolved to preclude the shutoff of protein synthesis.

Animals↗
PubMed1998

Accuracy of screening compression ultrasonography and clinical examination for the diagnosis of deep vein thrombosis after total hip or knee arthroplasty.

OBJECTIVE: To determine whether compression ultrasonography or clinical examination should be considered as screening tests for the diagnosis of deep vein thrombosis (DVT) after total hip or knee arthroplasty in patients receiving warfarin prophylaxis postoperatively. DESIGN: A prospective cohort study. SETTING: A single tertiary care orthopedic centre. PATIENTS: One hundred and eleven patients who underwent elective total hip or knee arthroplasty were enrolled. Postoperatively the warfarin dose was adjusted daily to maintain the international normalized ratio between 1.8 and 2.5. Eighty-six patients successfully completed the study protocol. INTERVENTION: Before they were discharged from hospital, patients were assessed for DVT by clinical examination, bilateral compression ultrasonography of the proximal venous system and bilateral contrast venography. RESULTS: DVT was found in 29 patients (34%; 95% confidence interval [CI] 24% to 45%), and 6 patients (7%; 95% CI 3% to 15%) had proximal DVT. DVT developed in 18 (40%) of 45 patients who underwent total knee arthroplasty and in 11 (27%) of 41 patients who underwent total hip arthroplasty. The sensitivity of compression ultrasonography for the diagnosis of proximal DVT was 83% (95% CI 36% to 99%) and the specificity was 98% (95% CI 91% to 99%). The positive predictive value of compression ultrasonography was 71%. In contrast, clinical examination for DVT had a sensitivity of 11% (95% CI 2% to 28%) and a positive predictive value of 25%. CONCLUSIONS: DVT is a common complication after total hip or knee arthroplasty. Compression ultrasonography appears to be a relatively accurate noninvasive test for diagnosing postoperative proximal DVT. In contrast, clinical examination is a very insensitive test. Whether routine use of screening compression ultrasonography will reduce the morbidity of venous thromboembolism after joint arthroplasty requires confirmation in a prospective trial involving long-term follow-up of patients.

Aged↗
PubMed1997

Successful treatment with ganciclovir of a HIV endstage patient with adrenal insufficiency.

We report on a 31-year-old AIDS patient who presented with rapid progressive fatigue, weakness, weight loss and hyperpigmentation. Endoscopy showed an ulcerous CMV gastritis with the histological hallmarks of this disease. In addition, laboratory tests revealed the constellation of an adrenal insufficiency with low plasma levels of sodium and increased levels of potassium and ACTH. After initiation of ganciclovir treatment, the CMV gastritis healed and the electrolyte abnormalities were resolved within 2 weeks. We assume that a CMV adrenalitis was treated in a reversible stage. The literature on CMV adrenalitis is reviewed to support this conclusion.

AIDS-Related Opportunistic Infections↗
PubMed1997

Disappearing bone disease (Gorham-stout disease): report of a case with a follow-up of 48 years.

A patient with osteolysis of the right hand after a metatarsal fracture at the age of 12 years is reported. The osteolysis progressed until the age of 21 years and was stable until the age of 59 years, when the patient died from a metastatic colon cancer. The article discusses the clinical, radiographic, and histologic features, and prognosis of idiopathic osteolysis (Gorham-Stout disease). Gorham-Stout disease is characterized by a non-familial, histological benign vascular proliferation producing lysis of the bone. The therapeutic options of Gorham-Stout disease is limited; radiotherapy has been used with success in single cases. Usually, the disease undergoes spontaneous arrest, as it occurred in our patient.

Fractures, Bone↗
PubMed1997

Ultrasonographic screening before hospital discharge for deep venous thrombosis after arthroplasty: the post-arthroplasty screening study. A randomized, controlled trial.

BACKGROUND: The clinical significance of asymptomatic deep venous thrombosis that develops after joint arthroplasty and the value of screening tests to detect thrombi are uncertain. OBJECTIVES: To determine 1) the rate of symptomatic deep venous thrombosis or pulmonary embolism occurring after hospitalization for joint arthroplasty and 2) the value of screening compression ultrasonography. DESIGN: Double-blind, randomized, controlled trial. SETTING: Tertiary care hospital. PATIENTS: 1024 patients undergoing elective total hip or knee arthroplasty who received warfarin prophylaxis. INTERVENTION: Patients were randomly assigned to undergo either bilateral compression ultrasonography or a sham procedure before hospital discharge. Patients with a diagnosis of asymptomatic deep venous thrombosis were treated after discharge with standard anticoagulant therapy; other patients had warfarin therapy discontinued at discharge. All patients were followed for 90 days. RESULTS: In the screening group, asymptomatic proximal deep venous thrombosis was detected in 13 of 518 patients (2.5%). Another 4 patients subsequently developed symptomatic proximal deep venous thrombosis, and 1 patient treated for asymptomatic deep venous thrombosis developed major bleeding, for a total outcome event rate of 1.0% (5 of 518 patients). In the placebo group, 3 patients developed symptomatic proximal deep venous thrombosis and 2 had nonfatal pulmonary embolism, for a total event rate of 1.0% (5 of 506 patients) (difference, 0 percentage points [95% CI, -1.2 to 1.2 percentage points]). CONCLUSIONS: In patients undergoing total hip or knee arthroplasty, the use of warfarin prophylaxis during hospitalization results in a very low rate of symptomatic deep venous thrombosis or pulmonary embolism after hospital discharge. The use of screening compression ultrasonography at hospital discharge does not seem to be justified in this setting.

Algorithms↗
PubMed1997

Presentation on class II MHC molecules of endogenous lysozyme targeted to the endocytic pathway.

We compared the processing and presentation of the model Ag, hen-egg white lysozyme (HEL) expressed in C3.F6 APC as a fusion protein to three different acid hydrolases: cathepsin D, to an unglycosylated form of cathepsin D, and to pepsinogen. As expected from the biology of mannose 6-phosphate (Man-6-P)-containing enzyme, cathepsin D-HEL was delivered to the endosomal/lysosomal system. In contrast, the unglycosylated cathepsin D-HEL was retained in ER/Golgi and some was found in lysosomes. Most of pepsinogen-HEL was rapidly secreted from the APC. All transfectants presented HEL epitopes to T cell hybridomas. Regardless of the main route of traffic of the proteins, the strong I-Ak binding epitope HEL 48-62 was well presented by all. The biochemical forms of this epitope were identical for all. Three other epitopes of HEL that bind I-Ak with less affinity were processed equally well by unglycosylated cathepsin D-HEL and HEL-Ld. The glycosylated cathepsin D-HEL was less efficient in generating the 114-129 epitope. Pepsinogen-HEL was the less efficient of all transfectants in presenting these subdominant epitopes. Soluble cathepsin D-HEL recovered from culture supernatant was strongly immunogenic when added to C3.F6. The uptake was inhibited by free Man-6-P, indicating that the surface Man-6-P receptor can effectively deliver proteins to the class II MHC system.

Animals↗
PubMed1997

The gamma(1)34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase.

In human cells infected with herpes simplex virus 1 the double-stranded RNA-dependent protein kinase (PKR) is activated but phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2) and total shutoff of protein synthesis is observed only in cells infected with gamma(1)z34.5- mutants. The carboxyl-terminal 64 aa of gamma(1)34.5 protein are homologous to the corresponding domain of MyD116, the murine growth arrest and DNA damage gene 34 (GADD34) protein and the two domains are functionally interchangeable in infected cells. This report shows that (i) the carboxyl terminus of MyD116 interacts with protein phosphatase 1alpha in yeast, and both MyD116 and gamma(1)34.5 interact with protein phosphatase 1alpha in vitro; (ii) protein synthesis in infected cells is strongly inhibited by okadaic acid, a phosphatase 1 inhibitor; and (iii) the alpha subunit in purified eIF-2 phosphorylated in vitro is specifically dephosphorylated by S10 fractions of wild-type infected cells at a rate 3000 times that of mock-infected cells, whereas the eIF-2alpha-P phosphatase activity of gamma(1)34.5- virus infected cells is lower than that of mock-infected cells. The eIF-2alpha-P phosphatase activities are sensitive to inhibitor 2. In contrast to eIF-2alpha-P phosphatase activity, extracts of mock-infected cells exhibit a 2-fold higher phosphatase activity on [32P]phosphorylase than extracts of infected cells. These results indicate that in infected cells, gamma(1)34.5 interacts with and redirects phosphatase to dephosphorylate eIF-2alpha to enable continued protein synthesis despite the presence of activated PKR. The GADD34 protein may have a similar function in eukaryotic cells. The proposed mechanism for maintenance of protein synthesis in the face of double-stranded RNA accumulation is different from that described for viruses examined to date.

Animals↗
PubMed1997

Adequate irradiation of the internal jugular lymph node chain: technical considerations.

PURPOSE: This research aimed to study the anatomic relationship between the internal jugular vein with the surrounding internal jugular lymph node chain and the underlying bony anatomical structures which are commonly used as landmarks for radiation therapy planning. METHODS AND MATERIALS: Twelve patients with carcinoma of the head and neck region were studied prospectively. Using our three-dimensional planning system, a beam's-eye view of the internal jugular vein was projected onto a lateral and anterior simulation film. Quantitative measurements were made in every case of the anatomic relationship between the internal jugular vein and the posterior border of the cervical vertebrae and sagittal midline. RESULTS: The distance between the posterior border of the internal jugular vein and the posterior border of the cervical vertebrae ranged between 0 and 2.5 cm. The distances between the sagittal midline and the medial border of the internal jugular veins ranged between 2 and 4 cm. CONCLUSION: To ensure adequate irradiation of the internal jugular lymph nodes, the posterior border of the lateral radiation therapy upper-neck fields should be placed at least 1 cm posterior to the posterior aspect of the cervical vertebrae. The midline block used in the lower neck anterior field should not exceed 2 cm in width.

Cervical Vertebrae↗
PubMed1997

The 52-kd protein as a target of intermolecular spreading of the immune response to components of the SS-A/Ro-SS-B/La complex.

OBJECTIVE: To determine whether immunization of healthy non-autoimmune mice with 52-kd SS-A/Ro induces a secondary antibody response to other components of the 48-kd SS-B/La-60-kd SS-A/Ro RNP complex and vice versa, since anti-52-kd antibodies have been invariably linked to these antigens in patients with Sjogren's syndrome and in mothers whose children have neonatal lupus. METHODS: Female BALB/c mice were immunized with 100 microg of 6xHis recombinant human 48-kd SS-B/La, 52-kd SS-A/Ro, or 60-kd SS-A/Ro proteins, or the 6xHis polypeptide control, each purified by Ni2+ affinity chromatography. Mice subsequently received booster injections with 50 microg of the same antigen every 10-21 days. Immune responses were measured by enzyme-linked immunosorbent assay (ELISA), immunoblotting of recombinant antigens, and immunoprecipitation of 35S-methionine-labeled in vitro translation products. RESULTS: Immunization with 48-kd SS-B/La resulted in anti-48-kd SS-B/La antibodies within 45 days, followed 10 days later by a secondary response to 52-kd SS-A/Ro, as measured by ELISA. Antibody spreading to 60-kd SS-A/Ro was not detected. Immunization with 52-kd SS-A/Ro resulted in rapid high-titer anti-52-kd SS-A/Ro responses within 27 days. Spreading to 48-kd SS-B/La occurred in only 1 mouse and 60-kd SS-A/Ro was detected in a minority of the mice after prolonged antigen exposure. Immunization with 60-kd SS-A/Ro led to anti-60-kd SS-A/Ro responses within 37 days, followed 3 months later by low-titer anti-48-kd SS-B/La and anti-52-kd SS-A/Ro antibodies. All primary immune responses were confirmed by immunoblotting and immunoprecipitation. While immunoblotting of the recombinant proteins revealed reciprocal intermolecular spreading in the majority of mice, immunoprecipitation clearly demonstrated that predominant spreading was generated after immunization with 48-kd SS-B/La, which consistently resulted in antibodies to 52-kd SS-A/Ro. CONCLUSION: The murine responses observed in the present study, demonstrating reciprocal intermolecular spreading to 48-kd SS-B/La, 52-kd SS-A/Ro, and 60-kd SS-A/Ro, support the linkage of 52-kd SS-A/Ro with the other proteins, despite their as-yet-undetected association in vivo. The marked recruitment of anti-52-kd SS-A/Ro responses elicited by 48-kd SS-B/La may provide a lead to exploring the physical interaction, direct or indirect, of 52-kd SS-A/Ro with the SS-A/Ro-SS-B/La RNP particle and its presentation to the immune system. These data should facilitate the establishment of a murine model of neonatal lupus.

Animals↗
PubMed1997

Hydrogen exchange properties of proteins in native and denatured states monitored by mass spectrometry and NMR.

The extent of deuterium labeling of hen lysozyme, its three-disulfide derivative, and the homologous alpha-lactalbumins, has been measured by both mass spectrometry and NMR. Different conformational states of the proteins were produced by varying the solution conditions. Alternate protein conformers were found to contain different numbers of 2H atoms. Furthermore, measurement in the gas phase of the mass spectrometer or directly in solution by NMR gave consistent results. The unique ability of mass spectrometry to distinguish distributions of 2H atoms in protein molecules is exemplified using samples prepared to contain different populations of 2H-labeled protein. A comparison of the peak widths of bovine alpha-lactalbumin in alternate solution conformations but containing the same average number of 2H atoms showed dramatic differences due to different 2H distributions in the two protein conformers. Measurement of 2H distributions by ESI-MS enabled characterization of conformational averaging and structural heterogeneity. In addition, a time course for hydrogen exchange was examined and the variation in distributions of 2H atom compared with simulations for different hydrogen exchange models. The results clearly show that exchange from the native state of bovine alpha-lactalbumin at 15 degrees C is dominated by local unfolding events.

Animals↗