Xeroderma Pigmentosum C: A Valuable Tool to Decipher the Signaling Pathways in Skin Cancers.

Xeroderma pigmentosum (XP) is a rare autosomal genodermatosis that manifests clinically with pronounced sensitivity to ultraviolet (UV) radiation and the high probability of the occurrence of different skin cancer types in XP patients. XP is mainly caused by mutations in XP-genes that are involved in the nucleotide excision repair (NER) pathway that functions in the removal of bulky DNA adducts. Besides, the aggregation of DNA lesions is a life-threatening event that might be a key for developing various mutations facilitating cancer appearance. One of the key players of NER is XPC that senses helical distortions found in damaged DNA. The majority of XPC gene mutations are nonsense, and some are missense leading either to the loss of XPC protein or to the expression of a truncated nonfunctional version. Given that no cure is yet available, XPC patients should be completely protected and isolated from all types of UV radiations (UVR). Although it is still poorly understood, the characterization of the proteomic signature of an XPC mutant is essential to identify mediators that could be targeted to prevent cancer development in XPC patients. Unraveling this proteomic signature is fundamental to decipher the signaling pathways affected by the loss of XPC expression following exposure to UVB radiation. In this review, we will focus on the signaling pathways disrupted in skin cancer, pathways modulating NER's function, including XPC, to disclose signaling pathways associated with XPC loss and skin cancer occurrence.

Diabetes supersedes dobutamine stress echocardiography in predicting cardiac events in female patients.

BACKGROUND: The many available choices for testing for coronary artery disease (CAD) brought about several questions regarding suitability of certain tests for different groups of patients and the prognostic value of obtained results in predicting events and mortality. The aim of this study is to describe the prognostic value of dobutamine stress echocardiography (DSE) results in predicting cardiac events and mortality in > or = 60-year-old females. METHODS: 49 women (> or = 60 years old) who were referred for DSE were included in the study. Data including CAD risk factors, and results of tests and a follow-up of events (MI, unstable angina, progression of CHF) and death. RESULTS: Eleven patients were considered to have a positive DSE result. There was no difference between DSE (+) and DSE (-) patients in cardiac events and cardiac death. However when interventions were included to events, analysis showed DSE (+) to have more overall events. Non-cardiac deaths and "all deaths" were 11 and 8 times more common among DSE (+) patients compared with DSE (-) patients p < 0.01. Multivariable logistic regression showed that diabetics and DSE (+) patients were 32 (p = 0.01) and 23 (p = 0.02) times more likely to have an event compared with non-diabetics and DSE (-) patients, respectively. CONCLUSION: DSE is a safe procedure to be used in > or = 60-year-old female patients and can provide informative prognostic information regarding all-cause deaths and cardiac events (including interventions) over a 4-year period. In addition we find that diabetes is a strong predictor of events regardless of DSE result.

Repeated doses of tissue plasminogen activator for failed thrombolysis: case report and review of the literature.

This article reports the first case of a patient presenting with acute myocardial infarction in whom a repeated dose of tissue plasminogen activator (t-PA) was able to achieve successful thrombolysis after a first dose of t-PA itself failed to do so. This case report presents an alternative approach for the treatment of patients who fail thrombolysis after an initial dose of t-PA, an approach that might be particularly useful in hospitals that do not have immediate access to advanced interventional services.

Ticlopidine-induced aplastic anemia and quick recovery with G-CSF: case report and literature review.

We report here a case of ticlopidine-induced aplastic anemia that responded to G-CSF and review the literature. An 83-year-old woman was started on ticlopidine for coronary artery disease after an episode of upper gastrointestinal bleeding secondary to aspirin. She developed aplastic anemia seven weeks after initiation of ticlopidine. She was hospitalised and received empiric antibiotic therapy and granulocyte colony stimulating factor (G-CSF). Her bone marrow started to recover quickly, and white blood cell and platelet counts returned to normal within three weeks. A review of medical literature revealed 20 similar cases of ticlopidine-induced aplastic anemia resulting in death in seven cases. G-CSF has been used previously with variable success. Ticlopidine is associated with serious, sometimes fatal hematological side effects. This risk should be seriously taken into consideration when prescribing ticlopidine. G-CSF may be helpful in the treatment of ticlopidine-induced aplastic anemia.

Is there a safe anticoagulation protocol for pregnant women with prosthetic valves?

We studied the outcome of 41 pregnancies in an attempt to identify an appropriate and safe anticoagulant regimen for pregnant women with cardiac valve prosthesis. The cumulative number of events: (neonatal death, premature deliveries, intrauterine fetal death and spontaneous abortion) was 66.6%, 20%, 12.5% and 20% in the Coumadin, Fraxiparine, Heparin and porcine valve groups, respectively. We conclude that in pregnant women with mechanical heart valves, low molecular weight heparin therapy is a superior strategy compared to warfarin.

Psychotic symptoms and age of onset in affective disorders.

Prevalence of hallucinations and delusions was studied in 1,763 patients with unipolar major depression, bipolar affective disorder, and schizoaffective disorder. The authors found that the presence of psychotic features was negatively associated with age of onset for the group as a whole, and bipolar affective disorder (manic or mixed type) specifically. The clinical implications of the findings are discussed.

Clinical presentation of enteric fever: its changing pattern in Kuwait.

The clinical experience with enteric fever (1985-89) at a general hospital in Kuwait is presented. There were 90 cases of typhoid and 10 cases of paratyphoid fever, with a mortality rate of 2%. Typhoid complications of bowel perforation, haemorrhage or septic shock were present in 5% and abortion in 2%. Neurological or psychiatric manifestations were a feature in 15%. Most infections were imported (78%). Despite rapid economic development, enteric fever may still be acquired locally but less frequently with time. This contributed to initial diagnostic uncertainty in 18% of cases, and especially in children. Another changing pattern emerged with the recent finding of five drug-resistant Salmonella typhi isolates, two in 1988 and three in 1989. Efforts are clearly needed to diagnose enteric fever more rapidly and to utilize new antibiotics for drug-resistant cases.

The prediction of suicide. Sensitivity, specificity, and predictive value of a multivariate model applied to suicide among 1906 patients with affective disorders.

Stepwise multiple logistic regression was utilized in an attempt to develop a statistical model that would predict suicide in a group of 1906 Iowans with affective disorders admitted to a tertiary care hospital. The risk factors identified by this approach included the number of prior suicide attempts, suicidal ideation on admission, bipolar affective disorder (manic or mixed type), gender, outcome at discharge, and unipolar depressive disorder in individuals with a family history of mania. However, the model failed to identify any of the patients who committed suicide. The results appear to support the contention that, based on present knowledge, it is not possible to predict suicide, even among a high-risk group of inpatients.

The prediction of recovery using a multivariate model in 1471 depressed inpatients.

Stepwise multiple logistic regression was used in an attempt to develop a statistical model which would predict "recovery" in a group of 1471 depressives admitted to a tertiary care hospital. Six variables identified by this approach included: Electroconvulsive therapy, personality disorder, chronicity, anxiety disorder, organic mental disorder, and dysthymia. The meaning and significance of the findings are discussed.

Hallucinations and delusions in 1,715 patients with unipolar and bipolar affective disorders.

The prevalence of hallucinations and delusions was studied in 1,715 patients with unipolar or bipolar affective disorders hospitalized at a tertiary care facility. The authors found that the presence of psychotic features was significantly associated with diagnostic subtype. Bipolar manics were more likely than primary depressives, secondary depressives, and bipolar depressives to have hallucinations and/or delusions; primary depressives were significantly more likely than secondary depressives to have psychotic features. Among psychotic patients, bipolar manics were more likely than the other diagnostic groups to have delusions only and less likely to have hallucinations only. Possible explanations for these findings are discussed.

The effect of somatic treatment and comorbidity on immediate outcome in manic patients.

Logistic regression was used to determine the association between clinical variables and outcome at discharge in a sample of 438 manics hospitalized at a tertiary care facility. In the total sample, and for males, treatment with electroconvulsive therapy (ECT) and lithium carbonate were positively associated with good outcome. Among females, ECT was positively associated and comorbidity negatively associated with good outcome. Comorbidity appears to be a potentially useful variable in predicting immediate response to treatment.

Effect of psychosis on suicide risk in 1,593 patients with unipolar and bipolar affective disorders.

The authors report suicide risk among 1,593 patients with major depression or bipolar disorder, 443 (27.8%) of whom were psychotic (260 bipolar and 183 unipolar). The subjects were followed for 0-14 years, and their suicide experience was compared with that of the state population. Eight (19.5%) of the 41 suicide victims were from the psychotic group. The psychotic and nonpsychotic subjects in each diagnostic group had similar risks for suicide. A higher risk for suicide was not found in the bipolar subjects. The authors conclude that among patients with major affective disorder psychosis per se does not predispose to suicide.

Predictors of immediate response in the treatment of mania: the importance of comorbidity.

Four hundred thirty-eight bipolar manics were admitted to an acute care psychiatric inpatient ward over a 12-year period. Eighty percent had good and 20% poor immediate outcome. Good outcome patients were characterized by short episode duration, older age of onset, a longer hospitalization, fewer suicide thoughts, and less psychiatric and medical comorbidity than the poor outcome group. Patients were divided into four treatment groups based on primary mode of therapy during index hospitalization: electroconvulsive therapy (ECT), adequate lithium, inadequate lithium, and neither treatment. Patients experiencing good outcome were more likely to be in the adequate lithium group and less likely to receive neither treatment. Regression analysis identified the absence of comorbidity, duration of lithium treatment more than 2 weeks, and duration of episode of less than 1 month as predictors of good outcome at hospital discharge.

Neonatal brucellosis.

Three Arab children with neonatal brucellosis are described. The first presented with late neonatal hyperbilirubinaemia, the second with a septicoemia-like picture and the third was born prematurely and presented with respiratory distress. The diagnosis of brucellosis was based on a positive blood culture and on a high or rising titre of antibodies to the Brucella organism. All the three neonates responded well to antibiotic therapy as monitored by a Brucella titre of less than 1:40 and a negative blood culture 10 weeks after the onset of therapy. The three mothers had Brucella infections during pregnancy and the Brucella agglutination titre of the breast milk was high. No Brucella microorganism was isolated from the breast milk. The mode of transmission of brucellosis in neonates is discussed.

The importance of Axis II in patients with major depression. A controlled study.

Using a naturalistic study design, we compared 76 depressed patients having a DSM-III personality disorder (PD) to a control group of 152 depressed patients with no personality disorder. The patients with major depressive disorder (MDD) and a PD were more likely to have had a younger age of onset, to have had prior hospitalizations, to have a longer duration of episode, to have reported more suicidal thoughts, and to have had more suicide attempts both before and after discharge. Patients with MDD and PD were also more likely to have a family history of alcoholism or antisocial personality and less likely to have dexamethasone nonsuppression, although the latter was not statistically significant. Patients with MDD and PD were less likely to receive electroconvulsive therapy (ECT), equally likely to have received antidepressants, and more likely to receive neither ECT nor antidepressants. Patients with MDD and PD had a poorer response to 'adequate' antidepressants, but a similar response to ECT and 'inadequate' antidepressants. Overall, 91 (60%) of MDD patients and 32 (42%) of MDD plus PD patients were recovered at hospital discharge (X2 = 6.43, P less than 0.025). We conclude that the presence of PD in patients with MDD is associated with a different clinical presentation, family history, and poor recovery at hospital discharge.