Wound botulism associated with black tar heroin

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is thought to play an important role in cellular immunological reactions. Expression can be induced by inflammatory cytokines in a wide variety of cells, including hepatocytes. OBJECTIVE: To compare the behaviour of ICAM-1 in liver diseases. PATIENTS AND METHODS: We assayed serum ICAM-1 (sICAM-1) in patients with hepatocellular carcinoma-associated liver cirrhosis, and compared them with a group of cirrhotic patients and controls. sICAM-1 values were also correlated with some biochemical parameters of liver function. Moreover, immunohistochemical localization of ICAM-1 was performed on liver tissue sections of patients with hepatocellular carcinoma, liver cirrhosis and a sample of normal liver. RESULTS: sICAM-1 levels were significantly higher in the hepatocellular carcinoma patients than in controls (P < 0.0001) and the cirrhosis group (P < 0.001). sICAM-1 values directly correlated with alanine aminotransferase, total bilirubin, alkaline phosphatase and gamma-glutamyltranspeptidase serum values (P < 0.05), with an inverse correlation with albuminaemia values (P < 0.05). There was no correlation with alpha-fetoprotein values, but sICAM-1 values were higher in hepatocellular carcinoma patients with large tumours (> 3 cm) than in those with small tumours (< 3 cm) (P < 0.04). Immunohistochemical localization of ICAM-1 was negative in normal liver tissue; positive staining for endothelial cells was found in chronic liver disease, while in hepatocellular carcinoma tissues, positive membrane staining was observed in hepatocytes and, to a lesser extent, at the cytoplasmic level. CONCLUSION: These results suggest that high serum levels of sICAM-1 are associated with severe liver disease, such as liver cirrhosis and hepatocellular carcinoma, and that they tend to increase with deteriorating hepatic function and tumour size.     

Etiology of endometrial cancer

Based on a survey of the literature, a summary of the etiology of endometrial cancer (EC) is presented. The effect of a number of expositions on the risk of developing EC, expressed as odds ratio or relative risk, are indicated. Combining these with the prevalence of the specific exposition allows calculation of the etiologic fraction (EF) for each risk factor. The etiologic fraction indicates the proportion of EC that would disappear if the exposition were eliminated. Obesity increases the risk of EC with a factor three to four. One quarter of Danish women of 60-70 years of age have a relative weight exceeding 1.2 times the ideal weight. The corresponding EF is 41%. Oestrogen substitution therapy is connected with an odds ratio of EC of 3.8 and an EF of 8%, anticipating that the lifetime prevalence of pure oestrogen substitution is 3%. On the other hand, oral contraceptives imply a reduction in EC of 14%, parity of 37% and cigarette smoking of 26%. It appears that the etiology of EC is multifactorial, and that a number of disposing and protecting factors are identified and quantified. The greatest prophylactic potential seems to be in reducing weight among obese women.     

Management of endometrial cancer

Preoperative assessment requires only endometrial sampling for diagnosis. Curettage is needed when endometrial sampling is unsatisfactory. Transvaginal ultrasonography may be useful in screening high-risk patients, as well as in assessing myoinvasion or cervical extension. Postsurgical pathologic prognostic factor analysis is most accurate in assigning risk for recurrence. Once the extent of disease is confirmed by the surgical staging procedure of hysterectomy, bilateral removal of the ovaries, and selective pelvic and periaortic node dissection, adjunctive therapy can be considered. Patients with low-risk stage IA and IB grade 1 disease require hysterectomy and removal of the adnexa. The poorer prognosis of patients with grade 2 or 3 histologic features in stages IB to IIB dictates considerations for adjunctive therapy. Soon randomized controlled trials will elucidate objectively what may be optimal adjunctive therapy. Ongoing prospective trials will clarify the role of operative laparoscopy. Current management guidelines are based on independent prognostic factors derived from analysis of surgicopathologic studies.     

Chemotherapy of metastatic endometrial cancer

Hereditary fructose intolerance (HFI) is a potentially fatal autosomal recessive disease of carbohydrate metabolism. HFI patients are deficient in aldolase B, the isozyme expressed in fructose-metabolizing tissues. The eight protein coding exons, including splicing signals, of the aldolase B gene from one American HFI patient were amplified by the polymerase chain reaction (PCR). Single-strand conformational polymorphism (SSCP) analysis and direct sequence determination were applied to the amplified fragments. The mutations in the patient's alleles were identified as a nonsense mutation (R59op) in exon 3 and a missense mutation (C134R) in exon 5. These mutations were confirmed by sequence determination of cloned PCR-amplified exons 3 and 5 from the patient. Allele specific oligonucleotide (ASO) hybridizations of amplified exons 3 and 5 showed the Mendelian inheritance of both mutations. Site-directed mutagenesis was used to generate an expression plasmid for the C134R mutation, and the mutant enzyme was expressed in bacteria. Assays of partially purified enzyme preparations showed that this missense mutation results in an apparently unstable enzyme that retains partial activity. This is the first evidence for a partially active aldolase B from an HFI individual with an identified mutation, and supports the hypothesis that adequate gluconeogenesis/glycolysis is maintained in HFI patients by the presence of partially active enzymes.     

Oestrogen therapy and endometrial cancer

The most controversial issue related to prolonged estrogen therapy is the possible relationship of this therapy to the etiology and pathogenesis of breast and uterine cancer. The imprecise nature of the relevant data does not allow full definition of the rish. To maintain proper perspective, smoking 20 cigarettes a day increases the risk of death from lung cancer 17 times; the risk from estrogens is less than that. There is no controversy over the use of estrogens for short-term relief of menopausal symptoms. The Mulley and Mitchell paper referred to was opinion based on no direct research and an inadequate knowledge of the literature. The early symptoms of estrogen dificiency, hot flushes and atrophic vaginitis, respond to short-term estrogen therapy, which in addition, provides a "mental tonic" effect. It is not justifiable to withhold such therapy from the normal informed patient requesting it, provided no contraindications exist. The patient should be reevaluated at frequent intervals, and the proper selection of drug, dosage, and therepeutic regimen administered. This can be accomplished, including research, through a menopause clinic.     

Endovaginal ultrasound to exclude endometrial cancer and other endometrial abnormalities

CONTEXT: Postmenopausal vaginal bleeding is a common clinical problem. Endovaginal ultrasound (EVUS) is a noninvasive diagnostic test that may help determine which women should undergo endometrial biopsy. OBJECTIVE: To determine the accuracy of EVUS in detecting endometrial disease in postmenopausal women with vaginal bleeding according to hormone replacement use. DATA SOURCES: Literature search of English-language and non-English-language articles published from 1966 through November 1996 using MEDLINE and by a manual search of bibliographies of published articles. STUDY SELECTION: Studies were included if they prospectively collected EVUS measurements of endometrial thickness prior to obtaining endometrial tissue for histologic evaluation in postmenopausal women with vaginal bleeding. Of 85 studies that included data on EVUS and endometrial histology, 35 were included in the meta-analysis and included 5892 women. DATA EXTRACTION: Articles were reviewed and independently selected and abstracted by 2 reviewers. Disagreement was resolved by consensus. DATA SYNTHESIS: The overall summary mean weighted estimates of sensitivity and specificity were calculated for thresholds of endometrial thickness from 3 to 10 mm. Using a 5-mm threshold to define abnormal endometrial thickening, 96% (95% confidence interval [CI], 94%-98%) of women with cancer had an abnormal EVUS result, whereas 92% (95% CI, 90%-93%) of women with endometrial disease (cancer, polyp, or atypical hyperplasia) had an abnormal result. This did not vary by hormone replacement use. However, the number of women with normal histology who had an abnormal EVUS result did vary by hormone replacement use. In women who were not using hormone replacement therapy, 593 (8%) with normal histological findings had an abnormal EVUS result (specificity, 92%; 95% CI, 90%-94%), whereas 1544 (23%) using hormone replacement therapy had an abnormal EVUS result (specificity, 77%; 95% CI, 75%-79%). For a postmenopausal woman with vaginal bleeding with a 10% pretest probability of endometrial cancer, her probability of cancer is 1% following a normal EVUS result. CONCLUSION: Endovaginal ultrasound has a high sensitivity for detecting endometrial cancer and other endometrial disease and can reliably identify postmenopausal women with vaginal bleeding who are highly unlikely to have significant endometrial disease so that endometrial sampling may be unnecessary.     

Factors associated with refractory cancer pain

Cancer pain can be effectively controlled in most patients by classical pharmacological treatment. We retrospectively studied the characteristics and factors associated with non responsive pain. Between 1989 and 1996, 1767 patients were referred to our pain center; 831 (47%) had cancer pain and from 787 evaluable cases 118 (15%) experienced non-controlled pain whereas good pain control was achieved within a few days in 669 (85%) patients. Gender, age, cancer type, metastasis, initial pain intensity, nociceptive or neuropathic components and administration of adjuvant therapies were similar in both groups. On the other hand, diffuse pain, abdominal pain, terminal care, near death and doses of strong opioids were significantly different. Factors associated with therapeutic failure were conflicts, life and complications and breakthrough pain. In the presence of refractory cancer pain the factors predictive of therapeutic failure should be identified in order to optimize individual pain treatment.     

PTEN mutation in endometrial cancers is associated with favorable clinical and pathologic characteristics

Mutation of the PTEN tumor suppressor gene is a frequent event in endometrial cancers. In other types of cancers, PTEN mutation has been associated with metastatic behavior and advanced stage. To examine the relationship between PTEN mutation and clinical features of endometrial cancers, we screened 136 cases for mutations in the nine exons and intronic splice sites of the PTEN gene, using single-strand conformation analysis, and aberrant bands were sequenced. Mutations were noted in 44 of 136 (32%) endometrial cancers, and two mutations were present in 8 cases. There were 36 cases with mutations resulting in truncated protein products, 6 cases with missense mutations in the phosphatase domain, 1 case with an in-frame deletion, and 1 case with a large insertion. Mutation of the PTEN gene correlated most closely with endometrioid histology; mutations were seen in only 5% (1 of 21) of serous/clear cell cancers compared with 37% (43 of 115) of endometrioid cancers (P = 0.004). PTEN mutation was associated with early stage, nonmetastatic disease and more favorable survival in both the entire group of 136 cases and in the 115 endometrioid cases. In addition, PTEN mutation correlated with other molecular features associated with favorable clinical behavior, including microsatellite instability and absence of p53 overexpression. Microsatellite instability was found in 60% of cases with PTEN mutations compared with only 25% of cases without mutations (P = 0.004). Overexpression of p53 was seen in only 14% of cases with PTEN mutations compared to 39% of cases without mutations (P = 0.006). In conclusion, PTEN mutation is associated with endometrioid histology and other favorable pathological, clinical, and molecular features rather than with increased metastatic potential as has been noted in some other types of cancers.     

Intermediate-risk endometrial cancer. A management approach

In the United States, endometrial cancer remains the most frequently diagnosed tumor of the female genital tract. The Gynecologic Oncology Group (GOG) has previously included patients with disease confined to the uterus and moderately or poorly differentiated tumors that invade at least half the myometrium in protocols designed for "intermediate levels of risk". Although such patients are ideally staged surgically, the role of adjuvant therapies such as postoperative pelvic irradiation remains unclear. This report offers a management approach for these women based on opportunities for enhanced local control with an acceptable level of morbidity according to supportive data from the available literature.     

Immune response associated with nonmelanoma skin cancer

The effect of antioxidants and reducing agents on glutamate-induced cytotoxicity was examined using PC12 cells. The antioxidants vitamin E, idebenone, and selegiline protected cells against the cytotoxicity observed 24 h after exposure to 0.5 or 10 mM glutamate, as determined by lactate dehydrogenase leakage, even when added 3 h after glutamate. The reducing agents, glutathione (GSH) and dithiothreitol (DTT), also provided protection against the cytotoxicity of glutamate. Preincubation of PC12 cells with the antioxidants mentioned above, or the incubation with those antioxidants after exposure to glutamate for 3 h, prevented the reduction of viability caused by glutamate. Cystine uptake was inhibited by exposure of cells to glutamate, as determined by L-[35S]-cystine uptake. Incubation of cells with 0.5 or 10 mM glutamate caused a marked decrease in cellular GSH levels, not prevented by antioxidants. The activity of GSSG reductase was decreased by glutamate and this inhibition was reverted in the presence of the reducing agents GSH and DTT. These results indicate that glutamate toxicity on PC12 cells results from the inhibition of cystine uptake with consequent GSH depletion and oxidative stress, suggesting that antioxidants may reduce the cellular damage in pathologic conditions associated with excessive glutamate release.     

Wound irrigation with tap water

OBJECTIVE: The study hypothesis was that irrigation with tap water is as efficacious as irrigation with sterile saline in removing bacteria from simple lacerations in preparation for wound closure. METHODS: The study was conducted in a laboratory rat model previously described in the literature for evaluating wound irrigation techniques. The study used a randomized, blinded crossover design using 10 animals. Two full-thickness skin lacerations were made on each animal and each wound was inoculated with standardized concentrations of a Staphylococcus aureus broth. Wounds were irrigated for 4 minutes with normal saline from a syringe or 4 minutes with tap water from a faucet. Tissue specimens were sampled from each laceration prior to and following irrigation. Bacterial counts per gram of tissue were determined for each specimen and compared pre- and postirrigation. RESULTS: Preirrigation bacterial counts were not significantly different for saline vs tap water specimens. The wounds irrigated with saline had a mean reduction in bacterial count of 54.7% (SD=+/-28%), while the wounds irrigated with tap water had a mean reduction in bacterial count of 80.6% (SD=+/-20%) (p < 0.05, 2-tailed, paired t-test). CONCLUSIONS: In this animal model, bacterial decontamination of simple lacerations was not compromised, and was actually improved using tap water irrigation. This is most likely due to the mechanical differences in the types of irrigation. In certain instances, such as with upper-extremity lacerations, tap water irrigation would likely be cheaper and less labor-intensive than irrigation with normal saline from a syringe.     

Estrogen replacement to women treated for endometrial cancer

Oestrogen replacement therapy in women treated for endometrial cancer has long been considered contra-indicated. Based on a review of the literature, which shows a low risk of recurrence during oestrogen replacement therapy in women treated for low-risk endometrial cancer, we advocate that this group of patients could be offered oestrogen replacement therapy and be provided with the benefits of prevention of cardiovascular disease and osteoporosis. Further studies are needed to investigate the survival and recurrence rates of high-risk patients treated with oestrogen replacement therapy.     

Dietary factors and the risk of endometrial cancer

BACKGROUND: Endometrial cancer is associated with overweight, but little is known on its possible relationship with specific aspects of diet. METHODS: The relationship between dietary factors and the risk of endometrial cancer was investigated in a case-control study conducted in Switzerland and Northern Italy on 274 patients with histologically confirmed endometrial cancers and 572 control subjects admitted to the hospital for acute nongynecologic disorders that were not hormone related, metabolic, or neoplastic. RESULTS: Significant direct associations were observed with (1) the total energy intake (odds ratio [OR] for the highest versus the lowest consumption tertile = 2.7) and, after allowance for energy intake, (2) the frequency of consumption of most types of meats, eggs, beans or peas, added fats (OR for total added fat = 2.5), and sugar (OR = 2.5). Significant protection, of the order of 40-60% reduction in the highest versus the lowest consumption tertile, was conferred by elevated intake of most vegetables and fresh fruit and whole grain bread and pasta. This was reflected in the low OR for the highest tertiles of intake of beta-carotene and ascorbic acid (OR for the highest versus the lowest consumption tertile after allowance for energy intake = 0.5). CONCLUSIONS: The current study suggests that, aside from the predictable adverse effects of overeating and consequent overweight, some qualitative aspects of the habitual diet may also be associated with the risk of endometrial cancer, chiefly, the intake of animal proteins and fat (directly) and of fresh fruit, vegetables, and fibers (inversely).     

Prognostic significance of tumour markers in endometrial cancer

BACKGROUND: Steroid 5 alpha-reductase is implicated in the pathogenesis of benign prostatic hyperplasia (BPH). We studied the in vitro and in vivo effects of FR146687, a new inhibitor of 5 alpha-reductase. METHODS: Two isozymes of rat and human 5 alpha-reductases were expressed in 293 cells. In vivo effects of drugs were evaluated on rat and dog prostates. Castrated immature rats were injected with testosterone propionate (TP) or 5 alpha-dihydrotestosterone propionate (DHTP) to induce growth of the ventral prostates. Testosterone and 5 alpha-dihydrotestosterone (DHT) contents in rat and dog prostates were measured by gas chromatography-mass spectrophotometry (GC-MS). RESULTS: FR146687 showed noncompetitive inhibition in both isozymes and no inhibitory effects on other steroid oxidoreductases. In mature rats and castrated immature rats treated with TP, FR146687 dose-dependently reduced ventral prostate and seminal vesicle weight at doses above 0.1 mg/kg, while castrated immature rats treated with DHTP were not affected by FR146687. FR146687 showed more potent reduction of rat prostates than finasteride. DHT concentration in the prostates was significantly reduced when FR146687 was administered to rats and beagles. CONCLUSIONS: FR146687 is a dual inhibitor for 5 alpha-reductase isozymes and significantly reduced the growth and DHT content in the prostate.