Imatinib-induced pseudoporphyria.

Imatinib, a synthetic tyrosine kinase inhibitor, is used as first-line therapy for chronic myeloid leukaemia. Imatinib treatment is associated with a variety of adverse effects, most of which are mild to moderate and generally abate after the first months of treatment. Cutaneous adverse reactions are often encountered in patients using imatinib. Pseudoporphyria is regularly associated with the use of medication, especially naproxen and other nonsteroidal anti-inflammatory drugs, but the list of culprits is expanding. We present a patient with imatinib-induced pseudoporphyria. Taking into account the rapidly growing use of imatinib, physicians should be aware of the possibility of imatinib-induced pseudoporphyria. Adequate photoprotection can improve treatment compliance.

Nutritional hormesis.

OBJECTIVE: Hormesis, the biological and toxicological concept that small quantities have opposite effects from large quantities, is reviewed with emphasis on its relevance to nutrition. RESULTS: Hormetic and other dose-response relationships are categorized, depicted, and discussed. Evidence for nutritional hormesis is presented for essential vitamin and mineral nutrients, dietary restriction, alcohol (ethanol), natural dietary and some synthetic pesticides, some herbicides, and acrylamide. Some of the different hormetic mechanisms that have been proposed are reviewed. CONCLUSIONS: The credence and relevance of hormesis to nutrition are considered to be established. The roles of hormesis in nutritional research and in formulating nutritional guidelines are discussed. SPONSORSHIP: The New York City Department of Health and Mental Hygiene.

Validation of a bulk tank milk antibody ELISA to detect dairy herds likely infected with bovine viral diarrhoea virus in New Zealand.

AIMS: To assess the sensitivity and specificity of a bulk tank milk (BTM) antibody enzyme-linked immunosorbent assay (ELISA) to detect likely infection of a dairy herd with bovine viral diarrhoea virus (BVDV). The ELISA was subsequently used to estimate the prevalence of likely infected herds in parts of the North Island of New Zealand. METHODS: BTM samples from 724 randomly selected dairy herds in the Waikato, Bay of Plenty and Northland regions of New Zealand were tested for BVDV antibodies. From this group, 20 herds were again randomly selected from each of the quartiles of the ELISA percentage inhibition (%INH) result. From each participant herd, serum from 15 randomly selected calves aged 6-18 months and 15 cows was collected and tested using an indirect blocking ELISA for BVDV antibodies. RESULTS: Among serum results from calves from 50 herds available for analysis, 34 (68%) herds were classified as likely non-infected (0-3 seropositive among 15 calves) and 16 (32%) as likely infected (5-15 seropositive among 15 calves). Receiver-operator characteristic (ROC) analysis identified an optimal cut-off for BTM of 80%INH associated with 81% sensitivity and 91% specificity for likely herd infection. The prevalence of BVDV antibodies in cows within herds and %INH for BVDV in bulk milk were positively correlated (p<0.01). The association between bulk milk %INH and the prevalence of BVDV antibodies in calves was stronger than the same association in cows. Based on the threshold of 80%INH, the 95% confidence interval (CI) for prevalence of likely infection in the 724 herds in the Waikato, Bay of Plenty and Northland regions of New Zealand was 12-17%. Vaccination against BVDV was not significantly associated with the likely infection status of the herd based on prevalence of BVDV antibodies among calves. CONCLUSION: An ELISA test result for BVDV antibodies in BTM >/=80%INH can be used as a threshold to indicate the presence of likely infection with BVDV in dairy herds in New Zealand, with 81% sensitivity and 91% specificity.

Short-term impact of carbon dioxide, helium, and gasless laparoscopic donor nephrectomy on renal function and histomorphology in donor and recipient.

BACKGROUND: Laparoscopic donor nephrectomy has the potential to increase the number of living kidney donations by reducing donor morbidity. However, studies have shown that raised intraabdominal pressure can result in transient renal dysfunction. Therefore, laparoscopically procured kidneys might be at higher risk for suffering a period of ischemia during pneumoperitoneum. The objective of this study was to investigate the short-term impact of pneumoperitoneum used for laparoscopic donor nephrectomy on renal function and histomorphology in donor and recipient. METHODS: EXPERIMENT 1: KIDNEY DONOR: Initially, 36 brown Norway (BN) rats were randomized for three procedures: 2 h of carbon dioxide (CO2) insufflation (8 mmHg), 2 h of helium insufflation (8 mmHg), and 2 h of gasless technique (0 mmHg). After this, a unilateral nephrectomy was performed in all the animals. EXPERIMENT 2: RECIPIENT: Subsequently, 36 donor BN rats were subjected to a similar insufflation protocol, but after nephrectomy, a syngeneic kidney transplantation (BN-BN) was performed. Urine and blood samples were collected on postoperative days 1, 3, 7, and 14 for determination of renal function. Subsequently, donor and recipient kidneys were removed for histomorphologic and immunohistochemical analysis. RESULTS: In both donors and recipients, no significant changes in serum creatinine, proteinuria, or glomular filtration were detected between the CO2, the helium, and the gasless control groups. In both experiments, histologic analysis of Kidney specimens did not show any deleterious effects from abdominal gas insufflation. Although kidney grafts exposed to CO2 showed significantly higher numbers of CD45+ leukocytes 3 days after transplantation, immunohistochemical analysis did not show significant differences in number of infiltrating cells (CD4, CD8, ED1, OX6, OX62) between the two insufflation groups and the gasless control subjects. CONCLUSIONS: Abdominal gas insufflation does not have an adverse effect on the renal function of the kidney donor 1 week after laparoscopic donor nephrectomy. No differences in renal function or histomorphology were detected between syngeneic kidney grafts exposed to pneumoperitoneum and gasless control subjects.

[Severe hypokalemia with paralysis in a patient with distal renal tubular acidosis as an initial expression of Sjögren's syndrome]. / Ernstige hypokaliëmie met paralyse bij een patiënte met een distale renale tubulaire acidose als eerste uiting van het syndroom van Sjögren.

In a 33-year-old woman with a recent flaccid paralysis of the arms and legs, laboratory tests demonstrated a severe hypokalemia with hyperchloremic metabolic acidosis and abnormally acidified urine. The urinary anion gap was positive in the presence of acidosis, thus establishing the diagnosis of distal renal tubular acidosis. The patient made a full recovery after potassium and alkali replacement. Further investigation revealed Sjögren's syndrome as the underlying cause.

Cytogenetic analysis of gemistocytic cells in gliomas.

Gemistocytes are glial cells characterized by voluminous, eosinophilic cytoplasm and a peripherally positioned, often flattened nucleus. Gemistocytes, usually present in anoxic-ischemic brains, are regularly encountered in glial neoplasms. The presence of gemistocytes in gliomas has been associated with an unfavorable clinical course, notwithstanding the low proliferative potential of these cells. It is not known whether gemistocytes residing in gliomas are dormant tumor cells, or alternatively, represent interspersed reactive glial cells. Whereas gemistocytic astrocytomas have been subject to various genetic investigations, no genomic analysis comparing individual cells in gliomas has been reported so far. In the present study, 3 astrocytomas, 3 oligodendrogliomas, and 3 mixed oligoastrocytomas, all harboring gemistocytic cells, were genetically analyzed by DNA in situ hybridization to paraffin-embedded, formalin-fixed tissue samples with optimal preservation of cellular morphology. To this end, probes for the centromeric regions of chromosome 7 and 10, known to show copy number aberrations in gliomas, were used. In addition, probes for centromeric regions of chromosomes 1 and 17 were used for the ploidy status of the tumors. The spot counts for the various chromosomes were statistically compared. Gains of chromosome 7 were found in 1 anaplastic astrocytoma, 1 anaplastic oligodendroglioma, and 1 anaplastic oligoastrocytoma. Loss of chromosome 10 was seen in 2 anaplastic astrocytomas, in 1 anaplastic oligodendroglioma, and in 1 anaplastic oligoastrocytoma. In 3 cases, significant differences in spot distributions between gemistocytes and non-gemistocytes were found, but the other cases showed no difference in spot distribution. It is concluded that, although many gemistocytic cells in gliomas may be considered reactive cells, in a subset of tumors, part of the gemistocytic cells should be considered neoplastic.

Expression of Epstein-Barr virus (EBV) transcripts encoding homologues to important human proteins in diverse EBV associated diseases.

AIMS: To examine the expression of Epstein-Barr virus (EBV) transcripts encoding proteins homologous to important human proteins in diverse EBV associated diseases. The proteins were: BHRF1 (homologous to Bcl-2), BDLF2 (homologous to cyclin B1), BARF1 (homologous to intercellular cell adhesion molecule 1 (ICAM-1)), and BCRF1 (viral IL-10 (vIL-10), homologous to human IL-10 (hIL-10)). METHODS: Six cases of oral hairy leukoplakia, seven of Hodgkin's disease, eight of T cell non-Hodgkin's lymphoma, and nine of nasopharyngeal carcinoma were examined at the mRNA level using either the reverse transcriptase polymerase chain reaction (RT-PCR) or nucleic acid sequence based amplification (NASBA). Different primer sets allowed the differentiation by RT-PCR of the latent (Cp/Wp driven) and lytic (Hp driven) transcripts of BHRF1. A specific NASBA reaction was developed for the detection of vIL-10 and BDLF2 transcripts and this was tested initially on cell lines and later on clinical samples. RESULTS: vIL-10 and BDLF2 were expressed almost exclusively in oral hairy leukoplakia, whereas BARF1 transcripts were present in all cases of nasopharyngeal carcinoma, with weak expression in one oral hairy leukoplakia and isolated cases of lymphoid malignancy. Both BHRF1 transcripts were detected across the range of tissues tested, but strong expression of lytic BHRF1 transcripts was seen only in oral hairy leukoplakia. CONCLUSIONS: vIL-10 and BDLF2 transcripts are expressed during productive EBV infection and are unlikely to be important in the pathogenesis of EBV associated malignancies. BARF1 appears to be expressed preferentially during viral latency and is more closely associated with malignant rather than benign epithelial proliferations. The alternative transcripts derived from the BHRF1 open reading frame may have very different roles during latent or productive infection.

Identification of vertical growth phase in malignant melanoma. A study of interobserver agreement.

Ninety-four H & E-stained slides of malignant melanoma were circulated to 6 pathologists in 2 university departments. For each slide, the growth phase of the lesion, Breslow thickness, and Clark level were determined by each observer. The aims of the study were to evaluate agreement between nonspecialist pathologists in identifying the vertical growth phase in malignant melanoma and to compare agreement for the growth phase with agreement for Breslow thickness and the Clark level. Our results show that although overall agreement for the growth phase is moderate, agreement between experienced observers is good. In fact agreement for the growth phase among this group was equal to the agreement for Breslow thickness. Overall agreement for Breslow thickness also was good but for the Clark level was only fair. These findings suggest that if the predictive value of the vertical growth phase proves to be robust, it will be used with an acceptable level of accuracy in routine diagnostic practice.

Production and reproductive responses to use of DairyMAN: a management information system for New Zealand dairy herds.

To assess the benefits of on-farm use of a computerized management information system (DairyMAN, Department of Veterinary Clinical Science, Massey University, Palmerston North, New Zealand) on seasonally calving herds of New Zealand, data for 144 herds using this system were compared with a stratified random sample of 294 herds using only the centralized National Dairy Database system during the season 1993 to 1994. Demographic, reproductive performance, and milk yield indices were compared. Herds using DairyMAN had superior reproductive outcomes, measured as a higher percentage (+8.4%) of cows calving during the desired seasonal period (critical in this seasonal system) and a higher percentage of cows (+9.7%) mated at the optimal time to achieve a concentrated calving in the following year. Multiple analysis of covariance was used to differentiate effects. The superior performance was not associated with differences in some of the more commonly used reproductive indices (efficiency of estrus detection, first service nonreturn rate, and pregnancy rate), but the data used in the study do not accurately reflect true performance. Herds using DairyMAN had more information on breeding performance because pregnancy data were available and natural breedings were recorded for a longer period. With cows of equivalent genetic merit, herds using DairyMAN produced more milk (+1.2 L/d per cow) indicating that users achieved better management of the herd through improved attention to managerial details. This improved production was associated with the adoption of DairyMAN but is not shown by this study to be a direct consequence of it. DairyMAN user herds were larger (245 cows) than were herds not using the system (181 cows), but this difference did not significantly affect the various outcomes measured.

Effects of calving induction on subsequent milk yield and reproductive performance of cows from seasonally mated New Zealand dairy herds.

AIM: To identify some production and reproductive effects of calving induction in seasonally calving herds. METHODS: Forty seasonally calving herds entered on the DairyMAN management information system and whose milk yield and reproductive data were recorded, including pregnancy diagnosis results, were included in the study. Cows with an induced parturition were compared with normally calving contemporaries that had the same lactation number and calved at the same time. RESULTS: Milk yield was 1.2 +/- 0.2 litres/cow/day less over the entire lactation for cows induced to calve, with the greatest difference being 2.5 +/- 0.4 litres/cow/day measured in early lactation. The effects on milkfat and protein yield were similar, with 0.04 +/- 0.01 kg/cow/day less milkfat (p < 0.0001) and 0.03 +/- 0.01 kg/cow/day less protein (p < 0.0001). A higher milkfat percentage (+ 0.09 +/- 0.04 %) (p < 0.0001) and protein percentage (+ 0.10 +/- 0.02%) (p < 0.0001) for cows that were induced to calve reduced the effect of a lower milk yield on milkfat and protein production. The first service conception rate for cows induced to calve was 54.4 +/- 3.3%, which was significantly less (p = 0.03) than for cows that calved normally (59.5 +/- 3.3%). Cows induced to calve had a pregnancy rate at the end of mating of 91.4 +/- 2.1%, which was also significantly less (p <0.0001) than for cows that calved normally (93.6 +/- 1.7%). The 21-day submission rates were not significantly different between groups. CONCLUSIONS: This study indicates that, under some New Zealand management conditions, the induction of calving is associated with reduced daily milk yield and inferior reproductive performance.

Effect of intraruminal monensin capsules on reproductive performance and milk production of dairy cows fed pasture.

Cows from three herds calving in spring that were fed on pasture were paired by herd, production index, predicted calving date, and age. One cow from each pair was allocated randomly to the treatment group and received a controlled-release capsule of monensin 1 mo prior to the start of AI. A random sample of 20 matched pairs of cows was selected within each herd to monitor BW and metabolic parameters. Treated cows produced more fat, protein, and liters of milk per day during the 2nd mo of monensin activity and produced a greater total milk volume than did control cows. Treated cows gained less BW during the 1st mo after treatment. No significant differences were identified in submission rates, overall pregnancy rates, or pregnancy rate to first or second AI. Blood urea nitrogen was elevated in the treatment group as a main effect, and NEFA were elevated in the 2nd and 3rd mo after treatment. There was no significant effect on blood concentrations of glucose, albumin, or BHBA.

Paradoxical response to heparin in 10 patients with ulcerative colitis.

OBJECTIVES: A patient with ulcerative colitis refractory to standard therapy was treated with heparin for a deep vein thrombosis. Paradoxically, rectal bleeding did not increase; instead, his colitis rapidly went into remission. The same effect occurred when this patient was later treated for a pulmonary embolism. On the basis of these observations and reports of a hypercoagulable state in ulcerative colitis, heparin was tested as a therapeutic agent in nine additional patients. METHODS: Nine of the 10 patients had ulcerative colitis poorly controlled on sulfasalazine and prednisolone. Two had associated thromboembolic disease, and one was on no medication. Patients were started on heparin in hospital, taught to self-inject subcutaneously, and discharged to continue on 10,000 U of unfractionated heparin twice daily. Current doses of sulfasalazine were maintained; prednisolone was tapered and stopped. Patients were carefully monitored for adverse side-effects. Sections of colonic mucosa from nine patients were examined for intravascular thrombosis of the mucosal blood vessels. RESULTS: Nine patients became asymptomatic (normal stool frequency, no rectal bleeding) on combined heparin and sulfasalazine therapy; one patient had a partial improvement in symptoms. Highly significant statistical differences between pre- and posttreatment mean scores were found for all disease parameters. Intravascular fibrin thrombi were identified in sections from six of nine patients. No serious complications were associated with this use of heparin. CONCLUSIONS: The heparin-linked remission of ulcerative colitis, observed by chance in our first patient, was followed by similar responses in eight of nine further patients. This suggests that, used as described, heparin may have a role in treating refractory ulcerative colitis.

Chemical-biological warfare: medical logistics and defense.

In this article, the authors discuss some of the hard realities of chemical and biological warfare defense in terms of the medical and medical logistics implications. In the opinion of the authors, there are no adequate defensive measures at present which would protect troops and sailors from the effects of either chemical or biological warfare tactics. An overview of the current world situation is presented, as well as some of the clinical and logistical responses to chem-bio war. The effectiveness of vaccinations or other medical approaches to protecting service members from chem-bio attacks is questioned in light of the technology and of the unpredictability in guessing the agent's strain or nature (e.g. viral, bacterial, or chemical). An analysis of Mission Oriented Protective Posture gear, gas masks, and other potential external protection devices reveals them to be inadequate, impractical, or expensive. In short, whether facing known war arsenals or unknown terrorist possibilities, the armed forces of the United States when meeting chemical or biological agents will be hard-pressed to protect and heal themselves, much less the nation's civilian population.