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Biomedical subjects

R Kowalski

Publications and source records attributed to R Kowalski.

At least 19 recordsLinked to original sources

The biocompatibility and osteoconductivity of a cement containing beta-TCP for use in vertebroplasty.

A new composite bone cement designated "G2B1" was developed for percutaneous transpedicular vertebroplasty. G2B1 contains beta tricalcium phosphate particles and methylmethacrylate-methylacrylate copolymer as the powder components, and methylmethacrylate, urethane dimethacrylate, and tetrahydrofurfuryl methacrylate as the liquid components. Biocompatibility and osteoconductivity were evaluated using scanning electron microscopy, contact microradiography, and Giemsa surface staining 4, 8, 12, 26, and 52 weeks after implantation into rat tibiae. To evaluate osteoconductivity, affinity indices (%) were calculated. Scanning electron microscopy and contact microradiography revealed that bone contact with G2B1 was attained within 4 weeks (affinity index: 50.2 +/- 11.8 at 4 weeks) and at most of the margin within 26 weeks (affinity index: 87.4 +/- 7.2 at 26 weeks). Specifically, G2B1 contacted bone via a wide calcium-phosphate-rich layer, and its degradation started within 8 weeks, mainly in the marginal area. Giemsa surface staining showed that there was almost no inflammatory reaction around the G2B1. These results indicate that G2B1 is a biocompatible and osteoconductive bone cement.

Animals↗

Gelatinases and serine proteinase inhibitors of seminal plasma and the reproductive tract of turkey (Meleagris gallopavo).

This study examined proteolytic enzymes and serine proteinase inhibitors in turkey seminal plasma with relation to their distribution within the reproductive tract and to yellow semen syndrome (YSS). Proteases of blood plasma, extracts from the reproductive tract, and seminal plasma were analyzed by gelatin zymography. We found a clear regional distribution of proteolytic enzymes in the turkey reproductive tract. Each part was characterized by a unique profile of serine proteolytic enzymes of molecular weights ranging from 29 to 88 kDa. The ductus deferens was found to be a site of very intense proteolytic activity. Two metalloproteases of 58 and 66 kDa were detected in all parts of the reproductive tract and seminal plasma. Using electrophoretic methods for detection of anti-trypsin activity, we found three serine proteinase inhibitors in turkey seminal plasma. Two inhibitors were found in the testis and epididymis and a third in the ductus deferens and seminal plasma. Blood plasma was characterized by the presence of two metalloproteinases and one serine proteinase inhibitor (of low migration rate) that were also detected in the reproductive tract. Amidase and anti-trypsin activities (expressed per gram of protein) differed for yellow and white seminal plasma. We concluded that turkey seminal plasma contains metalloproteases, serine proteinases, and serine proteinase inhibitors. The metalloproteases and one proteinase inhibitor are related to blood proteinases but the other two inhibitors and serine proteinases seem to be unique for the reproductive tract.

Animals↗

Metastatic adenocarcinoma to a pituitary adenoma.

Metastatic tumor to a pituitary adenoma has rarely been documented in the literature. We report a case of a 60-year-old man who presented with a history of progressive blurred vision and an incomplete homonymous hemianopsia. Magnetic resonance imaging showed a 5 cm heterogeneous mass which focally was contrast enhancing, involving the sella turcica and extending into the right cavernous sinus region. After worsening symptoms, repeat magnetic resonance imaging showed an increase in size of the lesion. Histologically, the mass consisted of a metastatic adenocarcinoma to a nonsecreting pituitary adenoma. The carcinoma stained focally positive with antibodies to carcinoembryonic antigen, cytokeratin 20, and p53 (60% of tumor cells), and did not stain with antibody to cytokeratin 7. The histologic appearance and immunohistochemical profile of the metastasis suggests a colorectal primary.

Adenocarcinoma↗

Incipient analysis of mesenchymal stem-cell-derived osteogenesis.

Tissue regeneration strategies invoke cell-based therapies for effective tissue formation. Current assessment of mesenchymal stem cell (MSC) directed bone regeneration during in vivo assays is dependent on histologic determination of bone formation. It was the aim of this study to determine the relationship between bone sialoprotein (BSP) expression and osteocalcin expression with subsequent osteogenesis occurring in MSC-based implants. RT-PCR assessment of human actin, collagen type I, BSP, and osteocalcin indicated that undifferentiated cells did not express BSP or osteocalcin. Three weeks following implantation, human BSP could be identified in RNAs isolated from the retrieved implants. For every implant from which human BSP cDNA was amplified, parallel implants harvested at 6 weeks demonstrated bone formation at the histologic level. This study confirms that, in the context of the severe combined immunodeficiency disease (SCID) mouse model, culture-expanded, cryopreserved human MSCs have osteogenic potential and demonstrates that implanted cell gene expression can reveal the early onset of bone formation.

Animals↗

An immune-based assay for HIV disease management.

Today, patients infected with HIV are monitored routinely for their levels of CD4+ T cells and viral load. Since either or both of these parameters are often discordant with the clinical course, the direct measurement of immune function to more accurately reflect clinical status is needed (Figure 3). The in vitro CMI test provides a rapid method for assessing cell-mediated immunity and is an important adjunct to the clinical management of these patients.

Biomarkers↗

Bose-stimulated raman adiabatic passage in photoassociation

We analyze coherent two-color photoassociation of a Bose-Einstein condensate, focusing on stimulated Raman adiabatic passage (STIRAP) in free-bound-bound transitions from atoms to molecules. This problem raises an interest because STIRAP has been predicted to be absent in the nondegenerate case [Javanainen and Mackie, Phys. Rev. A 58, R789 (1998)]. Nevertheless, we find that Bose stimulation enhances the free-bound dipole matrix element for an atomic condensate, and photoassociative STIRAP turns out to be a viable mechanism for converting an atomic condensate to a molecular condensate with near-unit efficiency.

Journal Article↗

Repeated administration of short infusions of bendamustine: a phase I study in patients with advanced progressive solid tumours.

PURPOSE: The cytotoxic agent bendamustine combines a purine-like benzimidazol and bifunctionally alkylating nitrogen mustard group. The drug has clinical antitumour activity in lymphoma, myeloma and breast cancer. In earlier dose-finding studies, the clinically tolerated dose for single-bolus bendamustine was 215 mg/m2; for fractionated therapy on 4 consecutive days it was 85 mg/m2. Anticholinergic symptoms, myelosuppression and cardiac dysrhythmia were dose-limiting. Our trial was designed to define the maximum tolerated dose of a short infusion schedule and to establish a recommended dose for ongoing and future clinical studies. METHODS: Patients with refractory malignant tumours qualified for the trial after written informed consent had been obtained. Bendamustine was given as a 30-min iv. infusion on days 1 and 8 of a 4 week cycle, with a starting dose of 100 mg/m2 and an increment per group of 20 mg/m2. RESULTS: Nineteen patients (13 male, 6 female; median age 57 years, range 37-74 years) were treated for one to two cycles with up to 180 mg/m2 bendamustine. At 160 mg/m2, fatigue grade 3 (NCI Common Toxicity Criteria) and dryness of the mouth grade 3 occurred in 2 patients, diarrhoea grade 3 in 1 patient; another patient with a history of myocardial infarction and arrhythmia developed a reversible total atrioventricular block after the first administration of 160 mg/m2 bendamustine. Other events, such as nausea/vomiting, loss of appetite, fever or chills, were not dose-limiting. Haematological toxicity was mild, except for sudden and long-lasting grade 3-4 lymphocytopenia, which occurred in all treatment cycles. Opportunistic infections were not observed. CONCLUSIONS: The maximum tolerated dose of a days-1 and -8 schedule of bendamustine, given as a 30-min i.v. infusion, is 160 mg/ m2; mouth dryness and fatigue are dose-limiting. The recommended dose for future trials is 140 mg/m2.

Adult↗

Production of TNF-alpha and bone resorbing activity by macrophages in response to different types of bone cement particles.

We have compared the capacity of clinically relevant wear debris from seven different cement types to activate macrophages to produce TNF-alpha, IL-1beta, IL-6 and bone resorbing activity in vitro. The bone cements were: CMW 1 original (PMMA only); CMW 1RO (1 microm BaSO4; 9.2%); CMW copolymer bone cement 1 (10 microm BaSO4; 10%); CMW copolymer bone cement 2 (1 microm BaSO4; 10%); Palacos R (10 microm ZrO2; 15.6%); CMW Calcium phosphate cement 20% (10 microm tri-calcium phosphate; 20%) and CMW calcium phosphate cement 30% (10 microm tri-calcium phosphate; 30%). Cement debris was produced aseptically using a simple configuration wear test. The majority of particles were in the size range 0.1-0.5 microm for each cement type. The cement particles were co-cultured with the U937 macrophage cell line at ratios of 10 and 100 microm3 particle volumes to macrophage cell numbers for 24 h. At the 10:1 ratio the particles had no effect on the cells. At the 100:1 ratio, the major cytokine produced was TNF-alpha and there were no statistical differences between the different types of cement debris. The bone resorption activity of the co-culture supernatants was significantly greater than the control (U937 cells without particles) for particles of CMW 1RO, CMW copolymer bone cement 1, CMW copolymer bone cement 2 and Palacos R (P < 0.05, ANOVA). However there were no statistical differences between the levels of bone resoprtion evoked by these four cement types. The CMW1 original and CMW calcium phosphate containing cements failed to induce the macrophages to elaborate bone resorption activity at the 100:1 ratio. These data suggest that the addition of radio-opaque additives to bone cement may increase the capacity of the debris to induce osteolysis.

Acrylic Resins↗

Weekly administration of bendamustine: a phase I study in patients with advanced progressive solid tumours.

BACKGROUND: The cytotoxic agent bendamustine combines a purine-like benzimidazol and alkylating nitrogen mustard group. The clinically tolerated dose for single bolus bendamustine is 215 mg/m2, for fractionated therapy on four consecutive days 85 mg/m2. The maximum tolerated dose of a day 1 and 8 (q4w) 30 min infusion schedule was recently found to be 160 mg/m2, mouth dryness and fatigue were dose-limiting. Our current phase I trial was designed to define the recommended dose of a new weekly short infusion schedule. PATIENTS AND METHODS: Patients with refractory malignant tumours qualified for the trial after written informed consent was obtained. Bendamustine was given as a 30-min i.v. infusion weekly for up to eight consecutive weeks. RESULTS: Twelve patients (8 male, 4 female, median age 57.5 years, range 42-64) were enrolled in this trial. At the starting dose of 80 mg/m2, two patients had dose-limiting toxicity (fatigue grade 3, mouth dryness grade 3, fever grade 4 Common Toxicity Criteria). No dose-limiting events were observed in six patients treated at 60 mg/m2. An intermediate dose level of 70 mg/m2 was studied in three younger, less heavily pretreated patients, was well tolerated and not associated with dose-limiting events. Haematological toxicity was mild except for grade 3-4 lymphocytopenia, occurring in 11 of 12 patients. Bendamustine was found to induce long-lasting panlymphocytopenia with predominant B-cell cytotoxicity. CONCLUSIONS: The maximum tolerated dose of weekly bendamustine given as a 30-min i.v. infusion is 80 mg/m2, mouth dryness, fatigue and fever are dose-limiting. The recommended dose for phase II trials is 60 mg/m2.

Adult↗

CD95 expression and apoptosis during pediatric HIV infection: early upregulation of CD95 expression.

Pediatric HIV infection is characterized by a progressive decline in CD4 T lymphocytes and faster disease progression than is typically seen in adults. Apoptosis, possibly mediated through the CD95 antigen, has been proposed as a mechanism for cell loss which eventually leads to immune dysfunction. In this study of peripheral blood lymphocytes from HIV-infected children, classified according to CDC immunologic categories, we found that the percentage of CD4 and CD8 T cells expressing CD95 and the percentage of lymphocytes undergoing apoptosis were increased in children with HIV infection and were greater in children from immunologic Category III as compared to those in Category I. Most striking was our observation that an increased percentage of CD95-positive cells appeared as early as 3 months of age, at a time when these children did not have elevated levels of apoptosis. These data demonstrate early upregulation of CD95 expression in HIV-infected infants, an abberation which may have profound implications for the pathogenesis of perinatally acquired HIV disease.

Age Factors↗

Case study: when restraints are the least restrictive alternative for managing aggression.

This article discusses the controversial use of restraints with a persistently violent adolescent on a child and adolescent psychiatry unit. The authors present an individualized program that used a series of ambulatory restraints on a long-term basis and prophylactically to contain the aggression of a psychotic girl. Clozapine was used concomitantly to control her psychosis. The prophylactic use of mechanical restraints allowed this teenager to be integrated into the milieu and to receive multiple treatments that the standard protocol precluded. This case underscores the difficulties in managing aggression when youths do not respond to standard protocols and do not conform to our assumptions about the least restrictive alternative. It is concluded that prophylactic mechanical restraint provided the least restrictive alternative to personal freedom for this teenager and had therapeutic benefit.

Adolescent↗

Molecular epidemiology of Staphylococcus aureus and Enterococcus faecalis in endophthalmitis.

Genomic DNA fingerprint analysis was performed on 39 Staphylococcus aureus and 28 Enterococcus faecalis endophthalmitis isolates collected from multiple clinical centers. Among 21 S. aureus genomic DNA fingerprint patterns identified, five clonotypes were recovered from multiple unrelated patients and accounted for 58.9% (23 of 39) of the isolates analyzed. Compared with strains having unique genomic DNA fingerprint patterns, the S. aureus clonotypes occurring more than once were more likely to result in visual acuities of 20/200 or worse (P = 0.036 [chi2 test]). In contrast to the S. aureus isolates, the E. faecalis endophthalmitis isolates were a clonally diverse population, enriched for the expression of a known toxin, cytolysin, which is plasmid encoded.

Bacterial Typing Techniques↗

Moderating effects of physical abuse and perceived social support on the potential to abuse.

This study investigated the moderating effects of perceived prepubertal social support on the relationship between prepubertal childhood physical abuse and child abuse potential as well as on the relationship between a childhood history of abuse and conflict and depth in adult relationships. Three hundred and sixty-nine undergraduate men and women were classified as abused or nonabused based on their responses to the Childhood History Questionnaire. Multiple regression analyses revealed interactions of social support and a childhood history of physical abuse on both the potential to abuse and the quality of participants' relationships with their parents. Differences between abused and nonabused individuals were obtained only under conditions of low perceived social support. When social support was perceived to be high, abused and nonabused individuals did not differ in the potential to abuse or in the ratings of the depth of their relationships with parents. Implications of these findings for the intergenerational transmission of abuse are discussed.

Adaptation, Psychological↗

Laboratory diagnosis of infection status in infants perinatally exposed to human immunodeficiency virus type 1.

Accurate and timely diagnosis of infection status in infants born to women infected with human immunodeficiency virus (HIV) is of paramount importance. The comparative accuracy of five diagnostic decision rules was evaluated in 208 HIV-exposed infants (32 infected, 176 uninfected) based on laboratory testing during the first 6 months of life. Diagnostic rules A and B, which required single blood samples analyzed by culture and polymerase chain reaction (PCR) (rule A) or culture, PCR, and p24 antigen detection (rule B) were more prone to incorrect diagnoses than were rules requiring 2 blood samples analyzed by a single assay (rule C) or combinations of culture and PCR (rules D and E). Rule D, which used PCR as the initial test, established the most useful algorithm: a positive PCR result followed by a positive culture in the second sample confirmed infected status, while two consecutive negative PCR results reconfirmed as negative at 6 months of age established uninfected status.

Blood↗

Lymphoepithelioma-like carcinoma of the lung.

Historically lymphoepithelioma was a term used to describe an undifferentiated mucosal carcinoma with a lymphocytic component arising only from the nasopharynx, although recently, lymphoepithelioma-like carcinoma has been found to occur as a primary tumor of the lung. Thus far, five patients have been documented as having this rare anatomical presentation. The patient that is being presented is the latest case of lymphoepithelioma-like carcinoma of the lung and will be compared clinically and histologically with the other four cases. The case is presented in order to discuss optimal methods of diagnoses and treatment for this condition.

Aged↗

Replication of ocular isolates of human adenovirus is serotype-dependent in rabbit corneal organ culture.

The goal of the present in vitro study was to determine the ability of unadapted human adenoviral ocular isolates to replicate in the rabbit cornea. Rabbit corneas grown in organ culture (24 well plate) were inoculated topically with 50 microliters (5 x 10(5) pfu) of different ocular adenoviral serotypes (ATCC and clinical isolates). Control wells (no cornea present) were inoculated in a similar fashion. Viral replication was determined by serial aliquots titrated on A549 cells. We demonstrated sustained viral replication over time of all isolates (100%) of Ad1, 2, 5, 6, 8, 9, 11 and 37 tested. No isolates (0%) of Ad3, 7A, 19, and 4 demonstrated replication in our model. Peak titers varied among successful serotypes from 10(2) pfu/ml (Ad11) to 10(5) PFU/ml (Ad5), and among different isolates of a given serotype. We conclude that the ability of unadapted human Ad serotypes to replicate in rabbit corneas was serotype-dependent, and that subgroup C (Ad1, 2, 5, and 6) appeared to be the most successful subgroup.

Adenoviruses, Human↗

Effect of spinal immobilization devices on pulmonary function in the healthy, nonsmoking man.

In the prehospital management of trauma, a variety of devices are used for immobilization of the spinal column during extrication and transport. Two of these commonly used immobilizers, the Zee Extrication Device and the long spinal board, use crisscrossing straps over the thorax to affix the patient to the device. Our study was designed to determine if these two devices alter pulmonary function in the healthy, nonsmoking man. We took 15 healthy, nonsmoking male volunteers and tested four pulmonary function parameters: forced vital capacity (FVC), forced expiratory volume in one second (FEV1), the ratio FEV1:FVC, and forced mid-expiratory flow (FEF 25%-75%). A Breon spirometer was used to test these functions both before and after the volunteers were strapped into the two devices. Three separate trials were given for each parameter and the best scores were used for data computation. Strap tension was controlled by placing a sphygmomanometer beneath each strap and adding tension to produce 10 mm Hg pressure. We found a significant difference (P less than .05) between prestrapping and poststrapping values for three of the four functions tested using the long spinal board: FVC (P = .0079), FEV1 (P = .0001), and FEF 25%-75% (P = .0252). Similarly significant differences were found for three of the four parameters using the Zee Extrication Device: FVC (P = .004), FEV1 (P = .0022), and FEF 25%-75% (P = .008). These differences reflect a marked pulmonary restrictive effect. The ratio FEV1:FVC can be normal or even slightly elevated with restrictive airway disease due to proportional reductions of each parameter. Correspondingly, we found no significant difference between prestrapping and poststrapping FEV1:FVC values (P greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Bystander/first responder CPR: ten years experience in a paramedic system.

The effectiveness of bystander CPR recently has been challenged. We undertook a ten-year retrospective review of our prehospital experience with witnessed cardiorespiratory arrest to ascertain save rates in patients receiving and not receiving CPR before paramedic advanced life support (ALS). Traumatic and poisoning arrests and children less than 18 years old were excluded. A total of 1,905 patients presenting to a paramedic system from November 1, 1973, to October 31, 1983, were bystander-witnessed arrests and attempted paramedic resuscitations. Four hundred five paramedic-witnessed arrests were excluded. One hundred eighty-two of 1,248 (14.6%) who had CPR initiated before paramedic ALS arrival were saves, compared to 38 of 252 (15%) who had no CPR initiated until paramedic arrival (P = NS). A save was defined as a patient discharged from the hospital. The respective save rates for coarse ventricular fibrillation were 148 of 628 (23.6%) (CPR before paramedic arrival) vs 35 of 151 (CPR delayed until paramedic arrival) (23.2%); electromechanical dissociation (EMD), 11 of 209 (5.3%) vs 0 of 38; asystole, 19 of 401 (4.7%) vs 3 of 61 (4.9%); and ventricular tachycardia, four of ten (40%) vs 0 of two. In this prehospital system, bystander/first responder CPR was found not to improve hospital discharge rates except in patients with initially documented rhythm of EMD.

Adult↗