Stevens-Johnson syndrome and toxic epidermal necrolysis at the University Hospital of the West Indies, Jamaica.

OBJECTIVE: Stevens-Johnson syndrome and toxic epidermal necrolysis are uncommon acute dermatologic disorders. The purpose of this study was to examine the frequency, aetiology and outcome of cases of Stevens-Johnson syndrome and toxic epidermal necrolysis admitted to the dermatology ward at the University Hospital of the West Indies. METHODS: This was a retrospective study looking at all patients who were admitted with a diagnosis of Stevens-Johnson syndrome, Stevens-Johnson syndrome/toxic epidermal necrolysis overlap syndrome and toxic epidermal necrolysis over a nine-year period. RESULTS: The results showed almost equal numbers of males and females. The drugs most commonly implicated were phenytoin and cotrimoxazole. The most common complications were hepatic impairment and ophthalmic complications. CONCLUSION: Stevens-Johnson syndrome and toxic epidermal necrolysis contribute significantly to morbidity and mortality of patients on the dermatology ward although mortality was low compared to other studies.

Cutaneous drug reactions in patients admitted to the dermatology unit at the University Hospital of the West Indies, Kingston, Jamaica.

OBJECTIVE: Cutaneous reactions are among the most common adverse reactions to drugs. The purpose of this study is to examine the aetiology and outcome of cutaneous drug reactions among patients admitted to the Dermatology Ward at the University Hospital of the West Indies. SUBJECTS AND METHODS: This was a retrospective study looking at all patients who were admitted with a diagnosis of a cutaneous drug eruption from January 1, 1997 to December 31, 2005. Data included patient demographics, date of admission to hospital, duration of hospitalization and a detailed drug history including any previous episodes of drug sensitivity. All drugs reportedly ingested by the patients up to three months prior to their cutaneous reaction were documented and the period of time between drug ingestion and the appearance of skin lesions was also noted. Clinical diagnosis, co-morbidities, histopathological diagnosis, final outcome and all ensuing disabilities were noted. The data retrieved were collated and analyzed using SPSS 12.0. RESULTS: The results showed a female to male ratio of 2.2:1. The categories of drugs most commonly implicated were antimicrobials followed by anti-epileptic drugs and nonsteroidal anti-inflammatory drugs. The most common form of drug eruption requiring admission was the exanthematous drug eruption followed by erythema multiforme, toxic epidermal necrolysis and Stevens-Johnson syndrome. CONCLUSION: In general, the causative agents identified and the types of drug eruptions were similar to those found in previous studies. However the anti-epileptic drugs, phenytoin and carbamazepine, ranked among the most commonly implicated drugs which differ significantly from other studies.

Space and time in the plant cell wall: relationships between cell type, cell wall rheology and cell function.

BACKGROUND: The biomechanical behaviour of plant cells depends upon the material properties of their cell walls and, in many cases, it is necessary that these properties are quite specific. Additionally, physiological regulation may require that target cells responding to hormonal signals or environmental factors are able to modulate these characteristics. ARGUMENT: This paper uses a rheological analysis of creep of elongating sunflower (Helianthus annuus) sunflower hypocotyls to demonstrate that the mechanical behaviour of plant cell walls is complex and involves multiple layered processes that can be distinguished from one another by the time-scale over which they lead to a change in tissue dimensions, their sensitivity to pH and temperature, and their responses to changes in spatial arrangement of the cell wall brought about by treatment with high M(r) PEG. Furthermore, it appears possible to regulate individual rheological processes, with limited effect on others, in order to modulate growth without affecting tissue structural integrity. It is proposed that control of the water content of the cell wall and therefore the space between cell wall polymers may be one mechanism by which differential regulation of cell wall biomechanical properties is achieved. This hypothesis is supported by evidence showing that enzyme extracts from growing tissues can cause swelling in cell wall fragments in suspension. IMPLICATIONS: The physiological implications of this complexity are then considered for growing tissues, stomatal guard cells and abscission cells. It is noted that, in each circumstance, a different combination of mechanical properties is required and that differential regulation of properties affecting behaviour over different time-scales is often necessary.

Estimates of the rate of acquisition of bacteraemia and associated excess mortality in a general intensive care unit: a 10 year study.

During a period of 10 years, 293 of 4270 admissions to the general intensive care unit (ICU) at Medway Maritime Hospital had 356 bacteraemias due to one of 14 microorganisms. Incidence of bacteraemia was least on the third day after admission, significantly greater on the fifth day and stable thereafter. From the fifth day the acquisition rate was 18.9 (16.5-21.3)/1000 bed-days, lower in those with an initial Acute Physiological Assessment and Chronic Health Evaluation II score (APII) <18, or admitted from the emergency room. A total of 1395 patients with no positive cultures in the first four days stayed in ICU for >or=5 days, and 204 subsequently had one or more bacteraemias. Hospital mortality in these patients was 45.6% (38.8-52.4), greater than in those with similar APII but sterile cultures [relative risk (RR): 1.30 (1.04-1.63) and matched controls, RR: 1.33 (1.09-1.63)]. Observed mortality was greater than predicted only in bacteraemic patients [RR: 1.31 (1.03-1.67)]. ICU-acquired bacteraemia was associated with an approximate additional absolute mortality of 11% contributing 0.5% to the 29.9% hospital mortality of all ICU admissions, 1.6% to the 34.6% of those staying >or=5 days, and 5.6% to the 35.9% of those remaining >24 days.

Contribution of acquired meticillin-resistant Staphylococcus aureus bacteraemia to overall mortality in a general intensive care unit.

During a period of 11 years, 77 patients had meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia > or =5 days after admission to the intensive care unit (ICU). Ten had no prior growth of MRSA, 13 had positive screens on admission and 54 initially tested negative for MRSA in ICU before positive blood culture. These 54 constituted 20.2% [95% confidence interval (CI): 15.6-25.0] of 267 who acquired MRSA > or =5 days after admission. Mortality among 77 patients with MRSA bacteraemia was 57.1% (46.0-68.2). Nineteen of these 77 patients with MRSA bacteraemia had growth of a second pathogen from blood. Those with only MRSA bacteraemia were each matched with five controls by diagnosis and initial Acute Physiological and Chronic Health Evaluation II score. Mortality was greater in bacteraemic patients [53.6% (40.5-66.7)] than in controls [31.8% (26.3-37.3)] [relative risk (RR) 1.69 (1.25-2.26), P < 0.01], implying an additional absolute mortality of 21.8% (8.0-40.1). Application of this estimate to all 77 patients suggests that ICU-acquired MRSA bacteraemia caused 17 (6-31) deaths, adding 0.3% (0.1-0.6) to the 30.1% hospital mortality of all admissions. Incidence of MRSA bacteraemia increased with length of stay, contributing an estimated 3.1% (1.1-5.7) towards 37.9% mortality of the 198 patients remaining > or =25 days. These data emphasise the importance of preventing initial MRSA colonisation/infection of long-stay patients.

The prevalence of mucocutaneous disorders among HIV-positive patients attending an out-patient clinic in Kingston, Jamaica.

OBJECTIVES: Skin disorders are thought to occur frequently in persons with HIV/AIDS. To our knowledge, there are no studies in the literature reporting on the spectrum and prevalence of skin disorders in HIV-positive patients in the Caribbean. This study focused on the prevalence and spectrum of skin disorders seen in a population of HIV-positive patients in Jamaica. METHODS: A 5-year retrospective study was conducted by reviewing the records of patients attending a HIV out-patient clinic at the University Hospital of the West Indies in Kingston, Jamaica. RESULTS: Two hundred and eighty-six (286) patients were included in the study. Skin and mucous membrane disorders were documented in 74% of the patients in this series. Inflammatory disorders comprised the largest category of skin disorders followed by fungal infections. The most frequently diagnosed dermatological disorders were papular prurigo, oral candidiasis, dermatophyte infections, herpes simplex infections and seborrhoeic dermatitis. Kaposi's sarcoma was rare. This pattern is similar to those reported from the African continent and other tropical countries. CONCLUSIONS: Dermatological disorders contribute significantly to the morbidity of HIV-positive patients and patterns of skin disorders are similar to those seen in other tropical settings.

Micro-spectrometer for fusion plasma boundary measurements.

In situ probes are being developed to make direct, spatially resolved measurements of the ion energy spectra in the edge of tokamak plasmas while being easily replaced and requiring minimal resources. The ion spectrometers will consist of a combined collimator and energy analyzer fabricated from silicon and mated to a detector to yield a form factor of approximately 2.0 cm × 1.5 cm × 0.2 cm. Results of fabrication and testing of the combined collimator and energy analyzer element are presented.

Transplacental immunization of the human fetus to tetanus by immunization of the mother.

Experimental studies in rats showed that immunization of the pregnant female led to the transplacental immunization of her fetuses. The possibility that this also occurred in humans was explored by immunizing 42 pregnant women with tetanus toxoid (2.5 or 5 Lf) in the fifth and eighth months of pregnancy and comparing the immune responses of their offspring with the responses of the offspring of 25 unimmunized mothers. Only the offspring of the immunized mothers were sensitized to tetanus. IgM antitetanus antibodies were in their blood before immunization with diphtheria, pertussis, tetanus vaccine (DPT), they had a more rapid (P less than 0.01) response to DPT immunization, and they were still highly sensitized (P less than 0.01) to tetanus 13 mo after birth. In addition, pregnancy had no immunosuppressive effect (P less than 0.05) on the responses of the mothers to tetanus toxoid. Thus, transplacental immunization occurs in humans; it enhances the response of the offspring to subsequent immunization, and it could be used to circumvent the necessity for immunization in early neonatal life.

Paclitaxel by 1-hour infusion: an active drug in metastatic non-small-cell lung cancer.

PURPOSE: Paclitaxel is an active single agent when administered as a 24-hour continuous infusion in the treatment of stage IV non-small-cell lung cancer. We evaluated the efficacy and toxicity of paclitaxel administered by 1-hour infusion in the outpatient setting to patients with stage IV or relapsed non-small-cell lung cancer. PATIENTS AND METHODS: Fifty-nine patients with stage IV or relapsed non-small-cell lung cancer were treated with 1-hour infusions of paclitaxel. The first 17 patients received a dose of 135 mg/m2 and the remaining 42 patients received 200 mg/m2. By random assignment, 31 patients received a single-day, 1-hour infusion of paclitaxel, and 28 patients received a 3-day, divided-dose schedule, with each dose administered by 1-hour infusion. Both regimens were repeated every 21 days. All patients received premedication with dexamethasone, diphenhydramine, and cimetidine. Cytokines were not routinely used. RESULTS: Thirteen of 53 assessable patients (25%) had partial responses to treatment. An additional five patients had minor responses. The median survival duration of the entire group was 8 months and the actuarial 1-year survival rate was 33%. Patients who received 200 mg/m2 of paclitaxel had a higher response rate than those who received 135 mg/m2 (31% v 12%, respectively). Six of 16 patients (38%) previously treated with cisplatin-based regimens responded to 200 mg/m2 of paclitaxel. No significant differences in activity were seen when the 1-day and 3-day paclitaxel schedules were compared. Paclitaxel was well tolerated at both doses and schedules, and no severe hypersensitivity reactions occurred. Only 18 of 154 courses (12%) given at 200 mg/m2 resulted in grade 3 or 4 leukopenia. CONCLUSION: Paclitaxel administered by 1-hour infusion is an active and well-tolerated new agent in the treatment of metastatic non-small-cell lung cancer. These results suggest that a paclitaxel dose of 200 mg/m2 is more effective than 135 mg/m2 and can produce responses in patients previously treated with cisplatin-based regimens. Incorporation into combination regimens is indicated.

Prolonged administration of low-dose, infusional etoposide in patients with etoposide-sensitive neoplasms: a phase I/II study.

PURPOSE: This trial evaluated the activity and toxicity of a prolonged schedule of low-dose, daily infusional etoposide in patients with etoposide-sensitive neoplasms. PATIENTS AND METHODS: Fifteen patients (non-Hodgkin's lymphoma, n = 10; small-cell lung cancer, n = 3; germ cell neoplasm, n = 2) were treated. Ten had received etoposide previously. Etoposide 18 to 25 mg/m2/d was administered by continuous intravenous infusion for at least 21 days, or until either leukocyte count decreased to less than 2,000/microL, platelets decreased to less than 75,000/microL, or tumor progressed. Plasma etoposide levels were monitored during infusion. RESULTS: Duration of therapy ranged from 21 to 560 days; uninterrupted infusion ranged from 21 to 153 days. Seven patients (47%) had an objective tumor response (six partial, one complete), with a median duration of 7 months (range, 2 to 19). Myelosuppression limited the infusion; however, only four patients had grade 4 leukopenia, and most tolerated infusions with mild to moderate leukopenia. Nine patients required RBC transfusions. Only one patient developed severe thrombocytopenia. Alopecia was universal; however, other grade 3 or 4 nonhematologic toxicities were not encountered. The mean serum etoposide concentration was 0.7 +/- 0.42 microgram/mL. Only three patients had serum etoposide levels greater than 1 microgram/mL. CONCLUSION: Etoposide administered as a low-dose continuous infusion is active in etoposide-sensitive neoplasms. Myelosuppression is the major toxicity, but seems reduced when compared with other schedules. Tumor cytotoxicity was demonstrated with plasma levels ranging from 0.5 to 1.0 microgram/mL. Chronic low doses of etoposide may be superior to the standard dose and schedule and further study of this issue is warranted.

A Role for the Stele in Intertissue Signaling in the Initiation of Abscission in Bean Leaves (Phaseolus vulgaris L.).

A combination of microdissection and viscometric endo-[beta]-1,4-glucanhydrolase assays was used to investigate if the early appearance of the abscission-related isoelectric point-9.5 endo-[beta]-1,4-glucanhydrolase in the stele of the pulvinus and abscission zone of the foliar abscission zone of Phaseolus vulgaris L. prior to cell separation (reported by E. del Campillo, P.D. Reid, R. Sexton, L.N.Lewis [1990] Plant Cell 2: 245-254) indicates that the vascular tissue of this region has a specific role in abscission. We find that no endo-[beta]-1,4-glucanhydrolase activity or cell separation is detectable in the abscission zone cortex if the abscission zone cortex is separated from the stele tissue. If the stele is separated from the abscission zone cortex after a lag period but again before any endo-[beta]-1,4-glucanhydrolase activity is present in the abscission zone cortex, then the enzyme is produced in the cortex and abscission ensues. We conclude that the cortex of the abscission zone is able to abscind independently of the vascular tissue only after the vascular tissue has begun to respond to abscission-promoting signals. We suggest that ethylene promotes formation of an abscission-permitting signal in the stele of the abscission zone and pulvinus, and that this signal is an essential elicitor for the synthesis of cell separation enzymes in the target cells of the abscission zone cortex.

Identification of a surface on the beta-propeller protein RACK1 that interacts with the cAMP-specific phosphodiesterase PDE4D5.

A strategy of mutagenesis followed by yeast two-hybrid assay was used to determine the sites on the WD-repeat protein Receptor for Activated C Kinase 1 (RACK1) necessary for it to interact with the cAMP-specific phosphodiesterase isoform PDE4D5. Analysis of deletion mutations demonstrated that WD-repeats 5-7, inclusively, of RACK1 contained the major site for interaction with PDE4D5. A reverse two-hybrid screen focusing on WD-repeats 5-7 of RACK1 isolated 11 single amino acid mutations from within this region that blocked the interaction. The ability of these mutations to block the interaction was confirmed by "pull-down" assays using bacterially expressed glutathione-S-transferase (GST)-RACK1 and mammalian cell-expressed PDE4D5. A model of RACK1 structure, based on the structural similarity of RACK1 to other beta-propeller WD-repeat proteins, indicated that the majority of the amino acids identified by mutagenesis are clustered in a discrete surface of RACK1. We propose that this surface of RACK1 is the major site for its interaction with the unique amino-terminal region of PDE4D5.

A phase I study of etoposide phosphate administered as a daily 30-minute infusion for 5 days.

PURPOSE: To determine the maximum tolerated dose, toxicities, kinetics, and disposition of etoposide phosphate when administered as a daily 30-minute infusion for 5 days. PATIENTS AND METHODS: Twenty-eight patients were enrolled in this phase I dose-escalation trial. Cohorts of patients received etoposide phosphate in etoposide equivalent doses of 50, 75, 100 and 125 mg/m2 intravenously for 30 minutes each day for 5 days. Pharmacokinetic sampling of both blood and urine was performed and concentrations of etoposide and etoposide phosphate were determined on day 1 of study for each patient and on day 4 of study for three patients receiving the 100 mg/m2 dose. RESULTS: The dose-limiting toxicity was reversible myelosuppression as evidenced by leukopenia and neutropenia. Toxicities seen were comparable to those expected from etoposide administration. With this schedule, the 100 mg/m2 dose was the maximum tolerated dose. Nonhematologic toxicities were generally mild. Two patients had major responses and three others had minor responses. Pharmacokinetic analyses revealed rapid (< 15 minutes) extensive conversion of etoposide phosphate to etoposide. Peak plasma etoposide concentrations and etoposide areas under the curve were proportional to the dose of etoposide phosphate administered. Etoposide kinetics were similar to those expected after a comparable dose of etoposide. CONCLUSIONS: Etoposide phosphate is a water-soluble pro-drug of etoposide that is rapidly converted to etoposide in vivo with a toxicity profile similar to etoposide. Etoposide generated from etoposide phosphate exhibits linear kinetics over a dose range of 50 to 125 mg/m2. When administered as a daily 30-minute infusion for 5 days, the dose-limiting toxicity is myelosuppression and 100 mg/m2 daily is the maximum tolerated dose.

Computerized tomography in the diagnosis of central and extrapontine myelinolysis.

In two patients the diagnosis of central pontine myelinolysis (CPM), suspected on clinical grounds, was supported by computerized tomographic (CT) sections made perpendicular to the pons, and confirmed on postmortem examination. Extrapontine myelinolysis was suggested on CT scans in both cases, and confirmed in one. Computerized tomography may prove to be a sensitive and accurate diagnostic test for CPM, and may aid in the detection of associated extrapontine lesions.

The effects of pregnancy in multiple sclerosis: a retrospective study.

We reviewed the medical records of 178 women with multiple sclerosis to evaluate the number of completed pregnancies, current disability status, and relationship of pregnancy to onset of MS symptoms. We found no differences in the long-term disability of women with no pregnancies, one pregnancy, or two or more pregnancies. Women who had initial symptom onset in pregnancy experienced less subsequent disability than women whose symptoms began before or after pregnancy. Therefore, pregnancy per se or number of pregnancies has no effect on subsequent disability.

Assessment of thrombocytopenic patients for splenectomy.

Platelet survival and splenic sequestration patterns were studied in 32 patients with thrombocytopenia using donor platelets labelled with chromium-51. A shorter mean platelet lifespan was observed in immune thrombocytopenia (ITP) (mean 12 hours) than in hypersplenism (mean 56 hours) or marrow hypoplasia (mean 102 hours). There was no such correlation between diagnosis and splenic sequestration. A biphasic survival curve was seen in nine of 22 patients with ITP. Thirteen patients underwent splenectomy with complete (9) or partial (4) response, but no consistent pattern of results was manifest. It is concluded that in vivo isotope studies are of little value in predicting the benefit of splenectomy in thrombocytopenic patients, although they may demonstrate the mechanism of the thrombocytopenia, in particular the biphasic survival curve revealing separate 'immune' and 'hypersplenic' components of platelet destruction in ITP.

Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women.

This study was conducted to investigate the effect of therapeutic estrogen on cytochrome P450 1A2-mediated metabolism in postmenopausal women using caffeine as a model substrate. Twelve healthy postmenopausal women underwent estrogen replacement therapy in the form of estradiol (Estrace). Estradiol was initiated at a dose of 0.5 mg a day and titrated to achieve a steady-state plasma concentration of 50 to 150 pg/ml. Caffeine metabolic ratios (CMR; paraxanthine/caffeine) were assessed both before and after 8 weeks of estrogen replacement. For the 12 subjects, there was a mean reduction in CMR of -29.2 +/- 25.0 (p = 0.0019). Consistent with previous results found in younger women, these results indicate that exogenous estrogen in older women may inhibit CYP1A2-mediated caffeine metabolism.

Granulocytic sarcoma of the small intestine preceding acute myelomonocytic leukemia with abnormal eosinophils and inv(16).

We report a case of preleukemic granulocytic sarcoma of the small intestine preceding the development of acute myelomonocytic leukemia with abnormal eosinophils and inversion of chromosome 16, inv(16)(p13q22). A literature review suggests that this is a recurring cytogenetic-clinicopathologic association and carries a favorable prognosis, especially if treated aggressively with antileukemic therapy at the time of diagnosis.

Psychiatric disorders and gynecological oncology: a review of the literature.

It is likely that patients with gynecological cancers are at risk for psychiatric disorders such as major depression and anxiety disorders. However, relatively little attention has been focused on studying these women. We review here papers that report rates and treatment of psychiatric illness in women with gynecological cancer. This small literature suggests that depression, anxiety, and adjustment disorders do occur with heightened frequency, and appear to worsen over the course of treatment persisting well after the initial diagnosis and therapy. Antidepressants are reported to be effective but compliance is often a problem. Limitations in this literature include a paucity of research specific to gynecological cancers, small sample sizes in reports that do exist, and minimal differentiation between the specific cancers and their rates of depression and anxiety. There is a clear need for more clinical and research attention to this at-risk population.