Free radical oxidation in patients with hypertrophic cardiomyopathy

As shown by the study of 27 patients with non-obstructive form of hypertrophic cardiomyopathy (HC), this disease is associated with a significant rise in the production of active oxygen forms by leukocytes, significant changes in the activity of enzyme antioxidant defense, unchanged lipid peroxidation, high total antioxidant activity of blood plasma. The patients received a complex of natural antioxidants varying by mechanism of action and glutaminic acid. Antioxidants produced a subjective clinical response, reduced incidence of cardiac arrhythmia, improved exercise tolerance. The response becomes still better in combination of antioxidants with conventional therapeutic tools.     

An ADP-ribosylation-factor(ARF)-like protein involved in regulated secretion

In higher plants, light enhances the activity of chloroplast fructose-1,6-bisphosphatase via a cascade of thiol/disulfide exchanges. We have examined the structural and functional role of seven conserved cysteine residues in the rapeseed (Brassica napus) enzyme by site-directed mutagenesis. After lysis of Escherichia coli cells, C53S and C191S variants partitioned mainly in the insoluble fraction whereas C96S, C157S, C174S, C179S, and C307S mutants were soluble. Homogeneous preparations of the latter hydrolyzed fructose 1,6-bisphosphate at similar rates in the presence of 10 mM Mg2+ but only C157S, C174S and C179S mutants were both efficient catalysts at 1 mM Mg2+ and nearly insensitive to dithiothreitol. These results demonstrate the contribution of Cys53 and Cys191 to the stability of the enzyme and the participation of Cys157, Cys174 and Cys179 in the reductive process responsive of the light-dependent regulation. Given that mutations at Cys96 and Cys307 neither destabilize the enzyme nor affect the reductive modulation, their function remains unknown.     

Influence of bromodeoxyuridine radiosensitization on malignant glioma patient survival: a retrospective comparison of survival data from the Northern California Oncology Group (NCOG) and Radiation Therapy Oncology Group trials (RTOG) for glioblastoma multiforme and anaplastic astrocytoma

PURPOSE: To examine the effect of treatment using Bromodeoxyuridine (BrdU) during radiation therapy on malignant glioma patient survival by comparing historical survival data from several large clinical trials. METHODS: A retrospective analysis of patient data from Radiation Therapy Oncology Group (RTOG) trials 74-01, 79-18, and 83-02 and the Northern California Oncology Group (NCOG) study 6G-82-1 was conducted. Patient data was supplied by both groups, and analyzed by the RTOG. Pretreatment characteristics including age, extent of surgery, Karnofsky Performance Status (KPS), and histopathology were collected; the only treatment variable evaluated was the use of BrdU during radiation therapy. Radiation dose, dose-fractionation schedule, use of chemotherapy, and/or type of chemotherapy was not controlled for in the analyses. Univariate and multivariate analyses were conducted to examine the potential treatment effect of BrdU on patient survival. RESULTS: Data from 334 patients treated with BrdU on NCOG 6G-82-1 and 1743 patients treated without BrdU on 3 RTOG studies was received. Patients were excluded from the review if confirmation of eligibility could not be obtained, if the patient was ineligible for the study they entered, if central pathology review was not done, or if radiotherapy data was not available. Patients treated according to the RTOG studies had to start radiotherapy within 4 weeks of surgery; no such restriction existed for the NCOG studies. To ensure comparability between the studies, patients from the NCOG studies who began treatment longer than 40 days from surgery were also excluded. The final data set included 296 cases from the NCOG studies (89%) and 1478 cases from the RTOG studies (85%). For patients with glioblastoma multiforme (GBM) the median survival was 9.8 months in the RTOG studies and 13.0 months in the NCOG trial (p < 0.0001). For patients with AA the median survival was 35.1 months for the RTOG studies and 42.8 months in the NCOG trial (p = 0.126). Univariate results showed consistent results favoring BrdU among patients over 30 years of age, across the extent of surgery, and for GBM patients. A proportional hazards regression model that included treatment, histopathology, KPS, age, and extent of surgery demonstrated that treatment with BrdU was included in the best model only for the GBM group of patients (risk ratio 0.83). CONCLUSIONS: Because of the heterogeneity of the treatment groups, including potentially important differences in pathology reviewers assessment of nonglioblastoma cases, differences in radiation dose and schedules, and chemotherapy during or after radiation, these analyses cannot provide the definitive answer as to whether BrdU given during radiation therapy improves survival in patients with malignant glioma. There does appear to be a favorable treatment effect seen in patients with GBM, with a lesser effect in patients with AA.     

Analysis of genome rearrangements in Streptomyces kanamyceticus mutants

Sarcoma consisting of dendritic reticular cells is one of the histiocytic sarcoma variants. In the case reported sarcoma affected axillary lymph nodes in a 20-year-old male. The tumor was surgically removed but recurred 2 years after radiation and polychemotherapy. The recurrent tumor was also surgically removed. Histology of the primary and recurrent tumors was similar. The tumors were studied electron-microscopically and immunohistochemically.     

Androgen-dependent beard dermal papilla cells secrete autocrine growth factor(s) in response to testosterone unlike scalp cells

The serum levels of choline decreased by approximately 50% in patients having a surgery under general as well as epidural anesthesia. The decrease is lasts for two days after surgery. Intravenous administration of succinylcholine, either by a single bolus injection or by a slow continuous infusion, increased the serum choline levels several folds during surgery. In these patients, a significant decrease in the serum choline levels was observed one and two days after surgery. In 16 pregnant women at the term, serum choline levels were higher than the value observed in 19 nonpregnant women. The serum choline levels decreased by about 40% or 60% after having a childbirth either by vaginal delivery or caesarean section, respectively. Serum choline levels in blood obtained from 9 patients with traumatic head injury were significantly lower than the observed levels in blood samples obtained from healthy volunteers. These observations show that serum choline levels increase during pregnancy and decrease during stressful situations in humans.     

An atypical presentation for primary sclerosing cholangitis

We describe the clinical course of a group of patients with primary sclerosing cholangitis who at presentation were diagnosed to have autoimmune hepatitis. The history of one such patient is described in detail. We also compare this atypical sclerosing cholangitis (group I) to typical sclerosing cholangitis (group II) and to autoimmune hepatitis with (group III) and without (group IV) cholestasis. At presentation, mean AST in groups I and III was similar and significantly higher than in group II (P < 0.05). Mean ALP was higher in sclerosing cholangitis than in autoimmune hepatitis but not significantly so. Triaditis was present in all patients in groups I, III, and IV. Piecemeal necrosis and multilobular collapse/fibrosis were equally frequent in groups I, III, and IV. Only the response to corticosteroids helped differentiate among groups. Groups III and IV responded by normalizing AST. In group I, AST improved, but never became normal. As ALP became disproportionately abnormal (ALP-predominant pattern), cholangiography was performed, and the diagnosis of primary sclerosing cholangitis was made in all group I patients. We recommend that cholangiography be performed early in patients with suspected autoimmune hepatitis who partially respond to corticosteroids and develop an ALP-predominant pattern.     

Confirmed abuse cases in public residential facilities for persons with mental retardation: a multi-state study

Our experience with 10 patients who suffered midshaft fractures of the femur and injuries to their ipsilateral hips has resulted in a treatment protocol that we believe can avoid unnecessary complications. The surgical protocol is a three-stage procedure based on (1) intramedullary nailing of the femur with interlocking for preserving the anatomic length and rotation of the femur; (2) treatment of the hip joint injury by means of open reduction and internal fixation of the acetabular fracture and/or reduction and fixation of the fractured femoral neck; and (3) repair of the extensor mechanism. Eight patients received this treatment and had fast recoveries. Union of the femoral fracture and full range of motion of the knee joint were observed within 3 months. In contrast, two patients who had received different surgical treatment had incomplete functional recoveries. This study offers a treatment protocol for ipsilateral disruption of the extensor mechanism, hip joint injury, and midshaft fracture of the femur in the multiply injured patient that can achieve full recovery with no complications. This relatively rare combination of injuries is definitely worthy of special attention.     

Total thoracic esophagectomy for esophageal cancer

BACKGROUND: Many current methods of esophageal resection have drawbacks that result in inadequate proximal resection, inadequate lymphadenectomy, and difficult gastric and splenic access. We describe a technique that allows reliable and safe access to the chest, abdomen, and neck. STUDY DESIGN: From 1988 to 1995, 113 patients (82 men; mean age 65.3 +/- 4.5 years) with carcinoma of the esophagus or esophagogastric junction (middle third in 34, lower third in 41, and cardia in 38) underwent total thoracic esophagectomy. The histology was adenocarcinoma in 71 (62.8%), squamous cell carcinoma in 32 (28.3%), and undifferentiated carcinoma in 10 (8.9%) of the patients; 57 tumors (50.5%) were stage III. The esophagus and stomach were mobilized through a left thoracoabdominal incision. After completion of the esophageal resection, the fundus of the stomach was sutured to the esophageal stump to allow later delivery of the stomach into the neck. The esophagogastric anastomosis was performed with continuous single-layer absorbable suture through a left oblique cervical incision. RESULTS: The mean duration of the operation was 309.2 +/- 47.9 minutes. Hospital stay ranged from 5 to 49 days (median, 12 days). The perioperative mortality rate was 4.4%. Anastomotic leak occurred in six patients (5.3%), one of whom died. The proximal resection margin was microscopically free of tumor in all cases, and with a minimum followup period of 18 months, there has been no anastomotic recurrence in any patient. Actuarial survival at 1 year was 63.4% +/- 4.9%, at 3 years 41.4% +/- 5.9%, and at 5 years 22.7% +/- 6.3%. CONCLUSIONS: Total thoracic esophagectomy through the left chest with a separate left cervical incision allows clear access to the esophagus and stomach and good tumor clearance. This procedure may be performed with a low rate of anastomotic leakage, a very low mortality rate, and no anastomotic tumor recurrence.     

Genotoxicity and cytotoxicity in male B6C3F1 mice following exposure to mixtures of 1,3-butadiene and styrene

1,3-Butadiene and styrene are oxidized, in part, by cytochrome P450 2E1 and have been shown to metabolically interact in rodents exposed by inhalation to mixtures of both compounds. Because the reactive metabolites of butadiene and styrene are thought to be responsible for the toxicity of each compound, metabolic interactions may alter the response in animals exposed to mixtures of butadiene and styrene compared with the response in animals exposed to butadiene alone or styrene alone. The purpose of this study was to quantitate alterations in genotoxicity and cytotoxicity in male B6C3F1 mice exposed to mixtures of butadiene and styrene. Male B6C3F1 mice were exposed to 6.25, 62.5, 200, or 625 ppm butadiene alone, 50 ppm styrene alone, or mixtures of 6.25, 62.5, 200, or 625 ppm butadiene and 50 ppm styrene. Genotoxicity was assessed by quantitating the frequency of micronucleated polychromatic erythrocytes in bone marrow. Cytotoxicity was assessed by counting total spleen and thymus cells and by quantitating the frequency of polychromatic erythrocytes in the peripheral blood. Butadiene and mixtures of butadiene and styrene were genotoxic in mice, as shown by a significant increase in the frequency of micronucleated polychromatic erythrocytes. The increased frequency following exposure to mixtures of butadiene and styrene was not significantly different compared with the frequency following exposure to butadiene alone. Styrene and mixtures of butadiene and styrene were cytotoxic in mice, as shown by significantly decreased number of spleen cells. Exposure to mixtures of butadiene and styrene with butadiene concentrations of 62.5 or 625 ppm significantly reduced the number of thymus cells. Exposure to 200 ppm or 625 ppm butadiene alone, or to mixtures of 200 ppm or 625 ppm butadiene and 50 ppm styrene, significantly reduced the frequency of polychromatic erythrocytes in the peripheral blood. The results of the study demonstrate that exposure to mixture of butadiene and styrene does not reduce the respective genotoxicity of butadiene or cytotoxicity of styrene.