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Biomedical subjects

R Novak

Publications and source records attributed to R Novak.

At least 37 records · Page 2Linked to original sources

Pathogenesis of pneumococcal pneumonia.

Pneumococcal pneumonia is the most severe of the common community-acquired pulmonary infections. The recent release of the complete DNA sequence reveals the entire capability of the bacteria and the current challenge is to map gene products to the mechanics of disease. This process will reveal antibiotic targets and protein vaccine candidates crossing serotype boundaries. Choline is a major constituent of surfactant and it is also a required nutrient for the pneumococcus. It appears that choline incorporated into the cell wall can bind the bacteria to the receptor for platelet activating factor, the gateway to invasion. The choline also serves as an antenna to which multifunctional proteins dock, thereby decorating the bacterial surface. This set of 12 choline binding proteins is subject to phase variation of expression resulting in display of different combinations of proteins that adapt the bacteria to survival on the mucosa versus the blood stream. These changes affect protective antigens, adhesions, and lytic proteins tying together the major elements of pneumococcal physiology: natural DNA transformation, adherence and invasion of host cells, and autolysis. Taking these components and building an understanding of disease is challenging. Clearly, the toxin pneumolysin is a major mediator of cell damage in the lung. Inflammation is also incited by cell wall components. The signal transduction pathways that explain pneumococcal inflammation are more complex than those for gram-negative endotoxin.

Animals↗

Modification of the Kock's pouch for bladder replacement.

AIM: To describe a modification of the Kock's pouch and present our clinical experience in its application. METHOD: After isolating an adequate ileal segment, the bowel is split by a longitudinal incision, with both ends remaining unopened for about 3-4 cm in length. Previously anastomozed ureters are inserted into the proximal end so that a nipple valve is created. The distal unsplit end serves for a direct anastomosis with the urethra. During the past 9 years, this surgery was performed in 41 patients who underwent radical cystectomy due to invasive carcinoma. Seventeen patients died for unknown reasons or were lost to follow-up. The remaining 24 were included in the follow-up for a period of 7 months to 6 years post surgery. RESULTS: Half of the patients included in the follow-up urinated spontaneously, with post void residuals less than 120 mL and no need for catheterization. Four patients did not urinate spontaneously and needed continuos catheterization, whereas 8 patients had post void residuals of 150-200 mL and needed catheterization once a day or once a week. None of the patients had a stricture at the site of ureteroileal anastomosis. CONCLUSION: We believe that our modification of the Kock's pouch makes the uretero-intestinal anastomosis much easier to perform; both ureters are inserted into the unsplit bowel end, thus preventing reflux; anastomosis with the urethra is performed under visual control; and direct anastomosis of widely opened distal end of the bowel reduces the possibility of scar stenosis.

Aged↗

Effect of long-term salmeterol treatment on exercise-induced asthma.

BACKGROUND: With long-term administration of salmeterol, the extent of protection afforded by the drug against experimental precipitants of asthma such as methacholine and adenosine may decrease. Whether this effect extends to a clinically relevant stimulus such as exercise is unknown. METHODS: We performed a random-order, double-blind, crossover trial in 20 patients with exercise-induced asthma. Each patient received inhaled salmeterol or placebo twice daily for a month, with a one-week washout period between treatments. The patients performed cycle ergometry while breathing frigid air 30 minutes after the morning dose and 9 hours later on the 1st, 14th, and 29th study days. The primary end point was the extent of the decrease in forced expiratory volume in 1 second (FEV1) 10 minutes after exertion. RESULTS: With placebo, significant airway narrowing developed at all times (mean [+/-SE] decrease from base line in FEV1, 19+/-2 percent in the morning and 18+/-2 percent in the evening). The morning dose of salmeterol attenuated the degree of bronchoconstriction at all times (decrease in FEV1 on day 1, 5+/-2 percent; on day 14, 10+/-3 percent; and on day 29, 9+/-3 percent; P=0.10). Its ability to act throughout the day, however, decreased with long-term administration (decrease in FEV1 from morning to evening on day 1, 6+/-2 percent; on day 14, 15+/-3 percent; and on day 29, 14+/-3 percent; P=0.003). CONCLUSIONS: Protection against exercise-induced asthma is maintained with long-term administration of salmeterol, but the length of time that the drug remains active after a single dose decreases.

Adrenergic beta-Agonists↗

Penicillin tolerance genes of Streptococcus pneumoniae: the ABC-type manganese permease complex Psa.

Downregulation of the major autolysin in Streptococcus pneumoniae leads to penicillin tolerance, a feature that is characterized by the ability to survive but not grow in the presence of antibiotic. Screening a library of mutants in pneumococcal surface proteins for the ability to survive 10x minimum inhibitory concentration (MIC) of penicillin revealed over 10 candidate tolerance genes. One such mutant contained an insertion in the known gene psaA, which is part of the psa locus. This locus encodes an ABC-type Mn permease complex. Sequence analysis of adjacent DNA extended the known genetic organization of the locus to include two new open reading frames (ORFs), psaB, which encodes an ATP-binding protein, and psaC, which encodes a hydrophobic transmembrane protein. Mutagenesis of psaB, psaC, psaA and downstream psaD resulted in penicillin tolerance. Defective adhesion and reduced transformation efficiency, as reported previously for a psaA- mutant, were phenotypes shared by psaB-, psaC- and psaD- knockout mutants. Western blot analysis demonstrated that the set of mutants expressed RecA, but none of them showed translation of the autolysin gene, which is located downstream of recA. The addition of manganese (Mn) failed to correct the abnormal physiology. These results suggest that this ABC-type Mn permease complex has a pleiotropic effect on pneumococcal physiology including adherence and autolysis. These are the first genes suggested as being involved in triggering autolysin. The results raise the possibility that loss of function of PsaA, by vaccine-induced antibody for instance, may promote penicillin tolerance.

ATP-Binding Cassette Transporters↗

In situ hybridization for detection of chicken anaemia virus in peripheral blood smears.

Blood smears, obtained from chickens known to be infected with or free from chicken anaemia virus (CAV), were tested to detect CAV DNA by in situ hybridization (ISH). A double-stranded, 1485 base-pair (bp) DNA probe was prepared employing polymerase chain reaction (PCR). The probe was labelled with digoxigenin or biotin by nick translation. In situ hybridization employing simple specimen preparation, using both digoxigenin- and biotin-labelled probes, provided a rapid and inexpensive method for diagnosis of CAV infection. Infection with CAV was detected by ISH prior to seroconversion by indirect immunofluorescence assay.

Animals↗

Seasonal abundance and distribution of mosquitoes at a rural waste tire site in Illinois.

The species composition, abundance, and distribution of mosquito larvae in tires were determined on 3 dates at a relatively large rural tire dump (about 300,000 tires) in southeastern IL (Jasper County). Several observations at this site differed from those in previous reports about mosquitoes in tireyards, including 1) a relatively high percentage of tires positive for Aedes triseriatus larvae in an open-field area, 2) a greater abundance of Culex pipiens than Cx. restuans in late-season collections, 3) a seasonal change in the distribution of Aedes atropalpus larvae in tires from open field and edge of woods areas, and 4) the presence of Ae. albopictus as a major late-season species. Ae. albopictus adults were captured in sod-baited gravid traps along the edge of a wooded riparian area 200 m from the tire pile.

Aedes↗

[Classical and current aspects of purulent meningitis].

Even today acute purulent meningitis is a life-threatening disease requiring immediate diagnosis and therapy. Despite the availability of bactericidal antibiotics, the mortality has not changed within the last 20 years. A therapeutic approach interfering specifically with the pathogenesis of inflammation is necessary in order to prevent long-term neurological sequelae and death associated with bacterial meningitis. In this paper we discuss the present level of understanding of antibiotics and adjunctive therapy, especially with regard to the molecular pathophysiological events occurring during a CNS infection.

Adolescent↗

Antiretroviral monotherapy in early stage human immunodeficiency virus disease has no detectable effect on virus load in peripheral blood and lymph nodes.

Initiation of antiretroviral monotherapy early in the course of infection with human immunodeficiency virus may result in a temporary slowing in the rate of disease progression; however, little is known about the virologic effects of early therapy. Virus load was measured in peripheral blood and lymph nodes from 16 antiretroviral-naive patients with a mean CD4 T lymphocyte count of 659 cells/microliter at baseline and after 8 weeks of either no treatment or zidovudine therapy. CD4 T lymphocyte counts and all virologic parameters examined remained unchanged regardless of zidovudine treatment status. Histopathology and virus distribution within lymph nodes remained constant between baseline and week 8 in each patient, indicating that the virologic and histologic parameters examined in a single lymph node are representative of a systemic process. Early antiretroviral monotherapy with zidovudine had no effect on virologic parameters in this group of patients with relatively high CD4 T lymphocyte counts and low measures of virus load at baseline.

Adult↗

An outcomes study of cochlear implants in deaf patients. Audiologic, economic, and quality-of-life changes.

OBJECTIVES: To investigate and quantitate the changes in economic, emotional, and health-related quality of life after cochlear implantation. SUBJECTS: Nine patients between the ages of 18 and 60 years who qualified for surgery. METHODS: Patients underwent assessment using four socioeconomic indicator scales administered preoperatively, and at 6 months, 1 year, 2 years, 30 months, and 3 years postoperatively. All patients continued to use their cochlear implants during the 3-year follow-up period. RESULTS: Uniform and systematic improvement in quality of life and psychologic well-being, and a steady increase in mean personal income for the group that underwent implantation, supporting the contention that cochlear implantation is a beneficial surgical procedure for profoundly deaf patients.

Adult↗

Urogenital wounds during the war in Croatia in 1991/1992.

There were 142 war injuries to the urogenital organs in 115 of 4,425 wounded patients treated at our clinical hospital during 18 months of warfare in Osijek, Croatia. Kidney injury was the most common (64 cases) and urethral injury (4) the least common, with a relatively large number of ureteral injuries (11). Two-thirds of the injuries were associated with other trauma, most frequently abdominal injuries. The mortality rate was high (15.6%), explained by the proximity of the battlefield and resulting rapid patient transport (average 52.21 minutes), which excluded the possibility of separating out the moribund cases, as well as the exceptional destructive power of modern explosives and firearms, and associated wounds of the vital organs. Of the wounded 60% were members of the Croatian armed forces, 1 was a member of the United Nations Professional Force and 39.13% were civilians. Surgical intervention was characterized by a tendency toward conservation and the avoidance of organ sacrifice. Thus, nephrectomy was performed in only a quarter of the cases of renal injury. Nevertheless, orchiectomy was performed in two-thirds of the cases of testicular injury. In 5 of 8 cases of corpus spongiosum injury the tunica albuginea was primarily reconstructed with free transplantation of the fascia lata. For ureteral injury resection with primary suture yielded good results in contrast to stents without resection in cases of ureteral wall contusion, which resulted in ureteral stenosis in our patients.

Adolescent↗

Comparative localization of carboxylesterase in F344 rat, beagle dog, and human nasal tissue.

BACKGROUND: Carboxylesterases (CE) exhibit high activity in the nasal mucosae and produce acid metabolites toxic to the olfactory epithelium following exposures to inhaled esters. The regional distribution and activity of CE have been studied in rodents, but no comparative studies have examined regional localization or activity in dog or human nasal tissues. METHODS: We determined the immunohistochemical distributions of CE in the nasal respiratory and olfactory mucosae of Beagle dogs, and the nasal respiratory mucosa of the human nose and compared these distributions to those in the F344 rat. RESULTS: In the dog respiratory mucosa, the greatest CE immunoreactivity was in the subepithelial glands and surface epithelial cells. In the olfactory mucosa, immunoreactivity was observed in the apical portion of the sustentacular cells, and in duct cells and acinar cells of Bowman's glands. This distribution is similar to that found in rat, except the subepithelial glands of the rat respiratory mucosa showed little to no immunoreactive CE. The human respiratory mucosa showed immunostaining in surface epithelial cells as well as glandular cells. Immunostaining in the human tissue samples was dramatically reduced in the presence of hyperplastic lesions and virtually eliminated in samples with squamous metaplasia. CONCLUSIONS: The data indicate that the distribution of CE is very similar in healthy nasal mucosae across the three species studied. However, the loss of CE immunoreactivity correlated with nasal epithelial lesions in the human samples suggests enzymatic activity may be compromised by insults to nasal tissues. Further studies of CE activity in animals following nasal insult could improve the ability to predict human responses to inhaled esters.

Adolescent↗

[Rectal neobladder. A 25-year experience].

On the experience of 153 cases of rectal bladder after cystectomy for cancer, the indications, technique and results of this operations are reported. Earlier, it was a method of choice as a bladder substitute. Today the indication is limited to female cysto-urethrectomy. Technique consists in rectum isolation and ureterorectal antireflux anastomosis; the sigmoid colon is pulled through behind rectum and between outer and inner layer of anal sphincter fixed on the perineum. The overall postoperative mortality is 7.8%, but in the last 5 years there was no mortality. The most frequent complications are sigmoid retraction and its partial necrosis. Micturition mostly is under control, but 14% of patients have a relative defecation incontinence.

Anastomosis, Surgical↗

Continent sigmoid bladder after cystectomy: 20 years' experience.

Twenty years' experience in the substitution of an isolated sigmoid segment after radical cystectomy for bladder carcinoma is described. The indication for surgery was isolated, non-transitional cell bladder cancer. The isolated sigmoid segment is placed longitudinally in the isoperistaltic direction. The study is made up of 73 cases. This operation does not make the procedure more radical since it does not increase survival for this illness. However, in relation to other bladder substitution methods, it guarantees a better quality of life after the operation.

Aged↗

Effect of positive-pressure ventilatory frequency on regional pleural pressure.

Regional lung ventilation is modulated by the spatiotemporal distribution of alveolar distending forces. During positive-pressure ventilation, regional transmission of airway pressure (Paw) to the pleural surface may vary with ventilatory frequency (f), thus changing interregional airflow distribution. Pendelluft phenomena may result owing to selective regional hyperventilation or phase differences in alveolar distension. To define the effects of f on regional alveolar distension during positive-pressure ventilation, we compared regional pleural pressure (Ppl) swings from expiration to inspiration (delta Ppl) and end-expiratory Ppl over the f range 0-150 min-1 in anesthetized, paralyzed, close-chested dogs with normal lungs. We inserted six pleural balloon catheters to analyze Ppl distribution along three orthogonal axes of the right hemithorax. Increases in regional Ppl were synchronously coupled with inspiratory increases in Paw regardless of f. However, at a constant tidal volume and percent inspiratory time, end-expiratory Paw and Ppl increased in all regions once a f threshold was reached (P less than 0.01). Supradiaphragmatic delta Ppl were less than in other regions (P less than 0.05), but thoracoabdominal binding abolished this difference by decreasing thoracoabdominal compliance. We conclude that the distribution of forces determining dynamic regional alveolar distension are temporally synchronous but spatially asymmetric during positive-pressure ventilation at f less than or equal to 150/min.

Animals↗

Effects of local chemotherapy and immunotherapy on the recurrence and progression of superficial bladder cancer.

409 cases of superficial bladder carcinoma (pTa, pTi, Tis) are reported. They are divided into three groups: 171 patients treated by TUR alone, 124 treated by TUR and local thio-TEPA, and 114 patients treated by TUR and BCG vaccine locally. It was found that the frequency of recurrence fell by 56.7, 41.9 and 26.3%, while the progression of the illness declined correspondingly by 19.8, 16.9 and 11.4%. In other words, in terms of recurrence and progression, the poorest results were found for the group treated by TUR only, and the best results were found with the TUR and BCG group.

Administration, Intravesical↗

Histologic analysis of placental tissue in first trimester abortions.

The value of histologic evaluation in the analysis of material from first trimester abortions is not completely defined. We prospectively analyzed placenta and decidua from 75 first trimester, spontaneous abortions to ascertain if morphologic features were predictive of karyotype. The histologic features analyzed included hydropic villus change, villus fibrosis, villus scalloping with trophoblastic invaginations, atypical stromal cells, aggregates of lymphocytes in placenta or decidua, and acute inflammation of placenta or decidua. Normal karyotypes were observed in 44 cases and abnormal karyotypes were demonstrated in 31. The presence of villus scalloping with trophoblastic invagination was significantly associated with abnormal karyotypes, particularly triploidy, and the demonstration of acute inflammation was seen significantly more often in cases with normal karyotypes. We conclude that histology can provide only a suggestion as to the likelihood of an abnormal karyotype; the findings are not specific enough to obviate the need for karyotyping in the individual case.

Abortion, Spontaneous↗

Transformation of the female breast during compression at mammography with special reference to the importance for localization of a lesion.

The effects of compression during mammography were studied in 187 breasts. The aims of this study were to investigate: 1) How the skin moves, 2) how the gland tissue is transformed, 3) if there is a relationship between outer and inner alterations and 4) the practical implications for aspiration biopsy. In this study, several experiments were carried out to investigate the effects of compression during clinical mammography in adult female breasts. The transformation of the breast during compression was investigated by means of external skin markings and internal markings using the biopsy needle and the hookwire at preoperative localization. The extent of the mammary gland was measured in the different standard projections during mammography. The calculation of the depth of a lesion during cranio-caudal compression was performed on the latero-medial radiographs. The result was checked with water-soluble radiographic contrast medium. The mean value of differences between observed and calculated depth was 3.7 mm. 1. The breast transforms during compression. 2. The biopsy needle in the breast and the barium markings on the skin incline ventrally in 96 per cent during latero-medial compression. The preoperative hookwire inclines ventrally in 92 per cent. 3. The extension of the gland parenchyma (the longest diagonal) is almost equal in all standard projections, including the medio-lateral oblique one. 4. The skin in the inframammary sulcus is firmly attached to the thoracic wall. This form of fixation determines principally the movements of the breast and limits the transformation during compression. 5. The movements of the skin are connected to the movements of the dense tissue, gland parenchyma. There is a connection between the ventral and descending inclination. These inclinations are caused by the same transformation of the breast. 6. Due to the regular movements of the breast during different compression directions, it is possible to predict the location of a lesion in three dimensions from standard mammograms.

Adult↗