Anti-atherosclerotic effect of microbial hyaluronate lyase from group B streptococci.

The effect of the microbial hyaluronic acid splitting enzyme hyaluronate lyase produced by Streptococcus agalactiae was investigated in vitro in human atherosclerotic plaque specimens and in vivo on Watanabe heritable hyperlipidaemic rabbits (WHHL) as an animal model for familiar hypercholesteraemia. The in vitro presence of the enzyme caused a partial destruction of the atherosclerotic plaque surfaces as well as releasing of glucuronic acid and solid calcium-containing materials from pieces of atherosclerotic plaques in human arteries. Accordingly hyaluronic acid seems to be the main component for anchoring of calcium deposits on the plaque surfaces. Repeated intravenous injections of hyaluronate lyase in WHHL rabbits resulted in a tendency of decreased formation of atherosclerotic plaques. The observed effects are discussed to be primary the result of the splitting of hyaluronic acid in the vessels.

Photodynamic therapy: a novel treatment for primary brain malignancy.

Providing therapy that conserves healthy brain tissue while effectively killing cancerous tissue remains a major challenge in the treatment of primary malignant brain tumors. The most common primary brain malignancies tend to recur despite intensive therapy, and the side effects of radiotherapy and chemotherapy can have considerable influence on health and quality of life. Photodynamic therapy (PDT) is a new technology being investigated to fulfill the need for a targeted cancer treatment that may reduce tumor recurrence and extend survival with few adverse effects. An investigational treatment, PDT employs wavelength-specific light in combination with a photosensitizing agent. The photosensitizing agent accumulates in tumor cells and is activated by nonthermal light, producing radical oxygen species that locally kill tumor cells. The selectivity of the process makes PDT appealing in the brain, where conservation of healthy tissue is vital. The most widely studied photosensitizer causes several weeks of ocular and cutaneous photosensitivity. Nursing care of the PDT patient includes intracranial pressure monitoring, neurological assessment, and intensive patient and family education. Many new photosensitizing compounds and varying methods of light delivery are being studied. This technology shows promise for the treatment of primary brain malignancies.

What to do when the doctor sees double: identical twins with nearly identical aneurysms.

SUMMARY: This report details the case of identical twins, both of whom had an aneurysm in the same anatomic location. Such aneurysms should be considered as a discrete subset of familial aneurysms. The implications for patient management are discussed.

Complementary characterization of a hyaluronic acid splitting enzyme from Streptococcus agalactiae.

A hyaluronic acid splitting enzyme of Streptococcus agalactiae was characterized by splitting mechanism, Michaelis-constant and inhibition type for sulfated hyaluronic acid: The enzyme splits hyaluronic acid as a hyaluronate lyase [EC 4.2.2.1]. The Km = 8 x 10(-4) mg ml-1 was determined with the influence of substrate inhibition constant Kiu = 2 x 10(-6) mg ml-1. Sulfated hyaluronic acid inhibits the enzyme in a partially non-competitive way. The inhibition constant is Ki = 5.47 x 10(-4) mg ml-1. The GBS-hyaluronate lyase cleaves hyaluronic acid as an endoglycosidase. The work is related with the intention to establish a hyaluronate lyase of microbial origin as a therapeutical enzyme replacing bovine hyaluronidase.

Using standardized patients to assess presentation of a dental treatment plan.

In this new era of relationship-based care, involvement in treatment planning and goal setting is a high priority for patient satisfaction. This study reports on the use of standardized patients (SPs) in training third-year dental students to gather dental, medical, and psychosocial information from patients and to involve the patient in the decision-making process leading to the dental treatment plan. Among the skill areas measured, students were most successful in gathering dental information, with 94 percent of the students obtaining the complete set. Students were least successful in identifying the patient's goals for treatment (81 percent of the students identified the patients' goals). Students were most challenged by discussing sensitive topics with patients such as grief-related depression (25 percent of the students recognized and discussed such topics). It is important that dental schools familiarize students with patient issues and teach them how to talk effectively to patients about personal issues and to incorporate those issues into a discussion of the treatment plan for the patient. Standardized patients can be used effectively toward this end.

Influence of the phosphorylation state on the biological activity of a low-molecular mitogen from group A streptococci.

A low molecular weight mitogen (LMP) from Streptococcus pyogenes strain NY 5 was successively purified by adsorption on phenylsepharose, chromatography on Resource S and Superdex G 30 and finally by affinity chromatography on antiphosphothreonine agarose. The N-terminal protein sequence of the mitogen was determined. The occurrence of phosphoamino acids was investigated by immunoassay using monoclonal antibodies. The LMP is a threonine-phosphorylated protein different of HPR protein of PTS-system, its mitogenic activity was lost after treatment with streptococcal protein phosphatase or alkaline phosphatase. The inactivated LMP was activated by phosphorylation with phosphokinase and ATP. The active LMP was also inactivated in streptococcal cultures secreting acid protein phosphatase during the phase of phosphate limitation.

Pituitary adenoma producing growth hormone and adrenocorticotropin: a histological, immunocytochemical, electron microscopic, and in situ hybridization study. Case report.

The authors report on the morphological features of a pituitary adenoma that produced growth hormone (GH) and adrenocorticotropic hormone (ACTH). This hormone combination produced by a single adenoma is extremely rare; a review of the available literature showed that only one previous case has been published. The tumor, which was removed from a 62-year-old man with acromegaly, was studied by histological and immunocytochemical analyses, transmission electron microscopy, immunoelectron microscopy, and in situ hybridization. When the authors used light microscopy, the tumor appeared to be a bimorphous mixed pituitary adenoma composed of two separate cell types: one cell population synthesized GH and the other ACTH. The cytogenesis of pituitary adenomas that produce more than one hormone is obscure. It may be that two separate cells--one somatotroph and one corticotroph--transformed into neoplastic cells, or that the adenoma arose in a common stem cell that differentiated into two separate cell types. In this case immunoelectron microscopy conclusively demonstrated ACTH in the secretory granules of several somatotrophs. This was associated with a change in the morphological characteristics of secretory granules. Thus it is possible that the tumor was originally a somatotropic adenoma that began to produce ACTH as a result of mutations that occurred during tumor progression.

Malignant transformation of ganglioneuroma into spinal neuroblastoma in an adult. Case report.

Ganglioneuroma is generally considered to be a benign tumor and potentially surgically curable. The authors present a case of a 21-year-old woman who underwent resection of a retroperitoneal ganglioneuroma and developed spinal neuroblastoma 11 years later. She has survived 10 more years with only recent development of metastases. To the authors' knowledge, this is the first report of malignant transformation of a ganglioneuroma into a neuroblastoma. Also, such long-term survival in an adult with spinal neuroblastoma has not been reported previously. This case raises the possibility of a dedifferentiating potential for ganglion cells in a ganglioneuroma or the presence of a long-term, quiescent form of neuroblastoma.

Contributors to dentists' job satisfaction and quality of life.

Every career has the potential for producing personal satisfaction and dissatisfaction, and much of that assessment is dependent on what an individual values in life. The purpose of this study was to identify factors that contribute to dentists' job satisfaction and the overall quality of their lives. Multiple regression analysis was performed to find the best set of predictor variables. After controlling for age, sex, and length of time in practice, the combination of variables that best predicted overall job satisfaction was income, respect, and patient relations (R2 = 57%). The combination of variables that best predicted overall quality of life, after again controlling for age, sex, and length of time in practice were income, professional time, and personal time (R2 = 83%). Although over half of the dentists surveyed are satisfied with their career, they are dissatisfied with their level of stress, professional environment (threat of malpractice litigation), and amount of personal time. Implications and recommendations are discussed.

Photodynamic therapy for malignant newly diagnosed supratentorial gliomas.

We report the use of photodynamic therapy (PDT) in the treatment of 20 patients with newly diagnosed malignant supratentorial gliomas. There were 10 males and 10 females; their mean age was 56 years and the mean Karnofsky score was 75. Eleven patients had glioblastoma multiforme (GBM) and 9 had malignant astrocytoma (MA). Intravenous porphyrin photosensitizer was administered 12-36 h prior to surgery and photoillumination. At operation all patients had the tumor subtotally resected followed by intraoperative cavitary photoillumination. Interstitial photoillumination using fibers with 2-cm diffusing tips supplemented the cavitary illumination in 3 patients. The total light energy delivered ranged from 570 to 4050 J (median = 1260 J). The energy density ranged from 15 to 110 J/cm2 (median = 32 J/cm2). All but two had postoperative radiation therapy (5000 cGy in 5 weeks). No untoward effects of radiation in conjunction with PDT were identified. There was 1 postoperative death and 1 patient had a persistent increase in postoperative neurological deficit. The median survival of these 20 patients with newly diagnosed malignant gliomas was 44 weeks with a 1- and 2-year survival of 40 and 15%, respectively. The median survival of these patients with newly diagnosed GBM was 37 weeks with a 1- and 2-year survival of 35 and 0%, respectively, and the median survival for MA was 48 weeks with a 1- and 2-year survival of 44 and 33%, respectively. Six patients with a Karnofsky score of > 70 who received a light dose of > 1260 J (mean energy density = 62 +/- 20 SEM J/cm2) had a median survival of 92 weeks with a 1- and 2-year survival of 83 and 33% respectively. Patients with malignant astrocytic tumors (GBM and MA) have a very poor prognosis. Nevertheless PDT is safe in newly diagnosed patients with supratentorial malignant gliomas who undergo postoperative radiation and appears to prolong survival in selected patients when an adequate light dose is used. Further improvement in survival may be expected with higher light doses.

Kinetics and regulation of erythrogenic toxins type A and C during growth of Streptococcus pyogenes.

The production of erythrogenic toxins type A (ETA) and C (ETC) is described as a function of growth kinetics. Group A streptococcal strains C 203 S and NY 5 were cultivated in yeast-peptone extract, Todd-Hewitt medium and a synthetic medium. Two main growth phases occurred during growth: a first logarithmic phase and a second linear phase. These phases were separated by a short stationary interphase caused by limitation of the amino acids L-serine and L-leucine. Maximum production of ETC was observed during the logarithmic phase, it was correlated to a high level of viable cells. ETA was produced mainly during the short stationary interphase. The production of ETC is regulated by L-isoleucine. A stagnation or reduction of the concentration of viable cells was observed during the interphase. The phosphate limitation caused during streptococcal growth induced expression of the extracellular protein phosphatase and surprisingly, of a serine proteinase activity. The association between these results and the pathogenicity of streptococci is discussed.

Photodynamic therapy for recurrent supratentorial gliomas.

We have used photodynamic therapy (PDT) in the treatment of 56 patients with recurrent supratentorial gliomas who had failed radiation therapy and who were candidates for palliative reoperation. There were 34 males and 22 females; their mean age was 41 years and the mean Karnofsky score was 79. Thirty-two patients had glioblastoma multiforme (GBM), 14 had malignant astrocytoma (MA), 6 had malignant mixed glioma (MM), and 4 had ependymoma (EP). Porphyrin photosensitizer was administered intravenously (i.v.) 12-36 hours prior to photoillumination. All patients had the recurrent tumor subtotally resected or cyst drained at surgery followed by intraoperative cavitary photoillumination. In 15 cases interstitial photoillumination using fibers with 2 cm diffusing tips supplemented the cavitary illumination. The total light energy delivered ranged from 440 to 4,500 Joules (J) (median = 1,800 J). The energy administered ranged from 120 to 150 J per fiber and the linear energy density ranged from 65 to 450 J/cm. The energy density ranged from 8 to 110 J/cm2 (median = 38 J/cm2). There were two postoperative deaths and three patients were left with a persistent increase in their postoperative neurological deficit. The post-PDT median survival of patients with recurrent GBM was 30 weeks with a 1- and 2-year actuarial survival of 18% and 0%, respectively. The median survival of patients with recurrent GBM from first diagnosis was 118 weeks with a 1- and 2-year actuarial survival of 82% and 57%, respectively. The post-PDT median survival of patients with recurrent MA was 44 weeks with a 1- and 2-year actuarial survival of 43% and 36%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinicopathologic features of primary and postirradiation cerebral gliosarcoma.

BACKGROUND: Gliosarcoma is an uncommon malignant brain tumor with mixed glial and mesenchymal elements. Experience is limited to case series, and pathologic data are disparate, leading to uncertainty about clinical features, management, and histogenesis. METHODS: A clinicopathologic review of 32 patients with survival analysis and immunohistochemical studies was performed including glial fibrillary acidic protein analysis, alpha-1-antitrypsin (alpha-1-AT) analysis, and smooth muscle actin (SMA) analysis. RESULTS: Twenty-five patients had primary gliosarcoma, whereas 7 developed gliosarcoma after irradiation for glioblastoma multiforme (GBM). Clinical features were similar to those of GBM. Most tumors were intraaxial and diffusely infiltrating by radiologic studies and at surgery. Median survival for primary gliosarcoma was 25 weeks overall, with patients who received irradiation surviving longer (46 vs. 13 weeks, P < 0.025). Gliosarcoma occurring after irradiation appeared hyperdense by computed tomography in five of seven cases, and median survival was 53 weeks. Primary gliosarcoma was a dimorphic tumor with malignant glial elements and features of malignant fibrous histiocytoma (MFH) or fibrosarcoma and one osteosarcoma. Smooth muscle actin labeled tumor vessels heavily, but in 15/25 primary cases, it extended to the surrounding spindle cells. The remaining cases appeared morphologically like MFH and tended to be positive for alpha-1-AT. Postirradiation gliosarcoma was fibrosarcomatous with positive SMA in 75% of the cases examined. CONCLUSIONS: Gliosarcoma behaves clinically like GBM, and survival may be improved by cranial irradiation of selected patients. Smooth muscle actin reactivity in sarcomatous areas suggests histogenesis in some tumors from the smooth muscle within GBM, whereas others may arise via different mechanisms including differentiation from a pluripotential precursor. Transformation of the smooth muscle within GBM may have therapeutic implications for antiangiogenesis agents.

Estrogen receptor gene expression in craniopharyngiomas: an in situ hybridization study.

Craniopharyngiomas are histologically benign epithelial neoplasms of the sellar region that frequently exhibit invasive and aggressive local growth. In this study, we have investigated the presence and cellular distribution of estrogen receptor messenger ribonucleic acid by in situ hybridization in 23 surgically removed craniopharyngiomas. All craniopharyngiomas studied, including 19 adamantinomatous and 4 papillary variants, uniformly expressed the estrogen receptor gene. In all cases, an intense estrogen receptor messenger ribonucleic acid hybridization signal was demonstrated; one localized exclusively to the epithelial cells of the tumor. Connective tissue and vascular elements were devoid of hybridization signal. Coexpression of the estrogen receptor protein was also studied by immunohistochemistry. Despite the relative abundance of estrogen receptor message in all cases studied, the estrogen receptor protein was focally but conclusively detected in only two tumors. The basis of this discrepancy is unclear. Progesterone receptor protein was also studied in all cases; however, its definitive presence was noted in only one instance and, in that case, in only occasional nuclei. The expression of the estrogen receptor gene by the proliferative epithelial elements of craniopharyngiomas raises the questions of a possible hormonal component to the genesis and/or progression of the craniopharyngiomas and a potential responsiveness to therapeutic hormonal manipulation.

Kinetics of growth and product formation in cultures from streptococci of groups A and C.

During growth of streptococci of Lancefield groups A and C in a culture medium containing glucose, yeast extract and peptone, two main growth phases occur: growth phase I and growth phase II (diauxic growth). They are separated by a short stationary phase (1st stationary phase). The diauxic growth is caused by transient limitations as well as the availability of new sources of the amino acids L-serine and L-arginine. Growth phase I consists of an exponential and a nearly linear part. These growth kinetics are reflected by the kinetics of gas metabolism as well as by product formation. Hyaluronic acid is formed during the nearly linear phase whereas the enzyme alkaline phosphatase, is exclusively excreted in the 1st stationary phase. Also carbon dioxide and L-lactate are mainly produced in a growth phase-dependent mode. In the late stationary phase (2nd stationary phase) more oxygen is consumed whereas the demand for oxygen in the 1st stationary phase is nearly zero.

Somatosensory evoked potential monitoring following severe closed head injury.

This paper describes the results of somatosensory evoked potential (SSEP) monitoring in 65 patients with severe head injury. Intracranial pressure (ICP) monitoring data were available for 63 patients, and arterial-jugular oxygen content (AVDO2) data for 52 patients. Eighty-nine percent of patients with no SSEP activity beyond 50 msec post-stimulus in either hemisphere died or were vegetative survivors (3 month Glasgow Outcome Score). All 17 patients with a good or moderate outcome had long latency cortical activity (i.e. > or = 70 msec post-stimulus) in both hemispheres. Among patients with absent activity in 1 hemisphere, 53% died and 47% were severely disabled (chi 2 = 40, p = 0.0000). In the latter group, age was a significant factor among patients who died or were severely disabled (p < 0.02). Forty-four of 65 patients had either clear-cut deterioration or improvement in SSEPs over the course of monitoring. There were no significant differences in peak ICP between patients with improving or deteriorating SSEPs. In contrast, those with deteriorating SSEPs had a significant drop in AVDO2, compared with patients with improving SSEPs (p < 0.01). Long-term continuous monitoring of SSEPs shows that following severe injury, neurologic function may undergo significant change in approximately two-thirds of patients. Furthermore, ICP does not appear to play a prominent role in neurologic deterioration. AVDO2 measurements indicate that deterioration is more likely associated with perturbation of cerebral oxidative metabolism. SSEP monitoring following severe head injury has proven prognostic value, and is recommended for patients who must be pharmacologically paralyzed for ICP or ventilator management.

Aspergillosis of the cranial base.

Aspergillus is an ubiquitous organism seldom pathogenic in normal hosts. Aspergillus osteomyelitis of the spine occurs rarely in immunocompromised patients as a result of hematogenous spread from distant foci. We present a case of Aspergillus osteomyelitis in the region of the jugular foramen in a previously healthy male with no antecedent event. He presented with dysphagia, hypophonia, and weight loss of several months duration. Diagnosis was delayed due to nonspecific results of various imaging tests. We review the clinical course of fungal osteomyelitis, including appearance on magnetic resonance imaging and computed tomography, culture characteristics, and gross appearance. Current treatment consists of surgical debridement and antifungal medications such as amphotericin B and itraconazole, and the efficacy of these are discussed.

The value of reoperation for recurrent glioblastoma.

To determine the value of reoperation alone (no further surgical procedures or radiotherapy), 43 patients (27 men, 16 women) with recurrent supratentorial glioblastomas who underwent a second craniotomy for recurrent tumour were reviewed retrospectively. The patients ranged in age from 27 to 66 years (median 53 years). All patients were treated initially by surgical resection and external radiation (50 Gy in 25 fractions through parallel opposed regional fields). In addition, 10 patients (23%) received chemotherapy, 3 patients (7%) received photodynamic therapy and 9 patients (21%) received interstitial brachytherapy postoperatively. Although none of the patients had further surgical procedures or radiotherapy after reoperation for tumour recurrence, 5 of the 43 did receive single-agent chemotherapy. The median survival after the first operation was 57 weeks. The median interval between first and second operations was 32 weeks. Median survival after reoperation was 19 weeks. An interval of more than 50 weeks between the two operations correlated with a significant (p < 0.05) increase in survival. The death rate for reoperation was 4.6%. The infection rate was 9.3%. The authors conclude that reoperation alone confers a modest but valuable increase in survival, especially if the interval between operations is greater than 50 weeks.