Pretransplant solid organ malignancy and organ transplant candidacy: A consensus expert opinion statement

Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.     

Delayed eye and other consequences from exposure to methyl isocyanate: 93% follow up of exposed and unexposed cohorts in Bhopal.

A follow up study three years after exposure to methyl isocyanate in 93% of exposed survivors and "control" residents in 10 Bhopali communities showed an excess of eye irritation, eyelid infection, cataract, and a decrease in visual acuity among the exposed people. Breathlessness was twice as common in the heavily exposed clusters as those with lower exposure, a trend that could not be explained by different age or smoking patterns (OR 2.05, 95% CI 1.36-3.08). Case referent analysis of outpatient attendances at Bhopal Eye Hospital, considering patients with severe refractive errors and astigmatism as "controls," showed a 40% increased risk of trachoma, 36% increased risk of other lid infections, and 45% increased risk of irritant symptoms among previously exposed people. "Bhopal eye syndrome" may thus include full resolution of the initial interpalpebral superficial erosion, a subsequent increased risk of eye infections, hyperresponsive phenomena (irritation, watering, and phlyctens), and possibly cataracts. It remains to be confirmed whether this reflects a more generalised disease as a consequence of previous exposure to methyl isocyanate or whether it is only the eye that is affected.     

Delayed eye and other consequences from exposure to methyl isocyanate: 93% follow up of exposed and unexposed cohorts in Bhopal

A follow up study three years after exposure to methyl isocyanate in 93% of exposed survivors and "control" residents in 10 Bhopali communities showed an excess of eye irritation, eyelid infection, cataract, and a decrease in visual acuity among the exposed people. Breathlessness was twice as common in the heavily exposed clusters as those with lower exposure, a trend that could not be explained by different age or smoking patterns (OR 2.05, 95% CI 1.36-3.08). Case referent analysis of outpatient attendances at Bhopal Eye Hospital, considering patients with severe refractive errors and astigmatism as "controls," showed a 40% increased risk of trachoma, 36% increased risk of other lid infections, and 45% increased risk of irritant symptoms among previously exposed people. "Bhopal eye syndrome" may thus include full resolution of the initial interpalpebral superficial erosion, a subsequent increased risk of eye infections, hyperresponsive phenomena (irritation, watering, and phlyctens), and possibly cataracts. It remains to be confirmed whether this reflects a more generalised disease as a consequence of previous exposure to methyl isocyanate or whether it is only the eye that is affected.     

Sequential clinico-histological studies in psoriasis following methotrexate therapy

Ten cases of psoriasis were studied to see the pattern of histological resolution and to evaluate clinico-histological correlation in psoriasis following weekly methotrexate therapy. Five sequential biopsies were taken in each patient. Scaling was first to regress followed by induration and erythema in 18, 26 and 35 days, respectively. Uniform granular layer appeared in 4 days, stratum corneum became orthokeratotic in 7 days, mitotic activity got restricted to basal layer in 7 days and rete ridges elongation was reduced to half in 11 days. Mild acanthosis, cellular infiltrate and vascular dilatation pesisted even after full clinical regression. Interestingly, 5 out of 10 biopsies revealed increase in cellular infiltrate and oedema after first methotrexate pulse.     

Alterations in the conjunctival bacterial flora following a single dose of azithromycin in a trachoma endemic area

BACKGROUND/AIMS: The World Health Organisation has recommended repeated mass treatment of children in trachoma endemic areas with oral azithromycin. While chlamydia, the causative agent of trachoma, remains universally sensitive to azithromycin, there is concern that large scale programmes may alter the bacterial flora and induce resistance in streptococcal species. In this study the effect of a single dose of azithromcyin on the prevalence, species distribution, and resistance of conjunctival bacterial flora was determined. METHODS: Baseline and 14 day follow up bacterial cultures were taken from the conjunctivae of 121 children who reside in a trachoma endemic area of Nepal. 91 children were treated with azithromycin at baseline and 31 children received deferred treatment at the 14 day follow up. RESULTS: Although the prevalence of bacterial pathogens decreased significantly with azithromycin treatment, a significant change in the distribution of specific bacterial pathogens could not be demonstrated. Streptococcal resistance to azithromycin was found significantly more frequently after treatment. No change in the prevalence, distribution, or resistance pattern was found in the untreated control group. CONCLUSION: Repeated mass treatment of trachoma endemic areas with oral azithromycin will have an effect on bacterial flora. However, further work needs to be done to determine if this will have any clinical relevance.     

Desensitization of human breast-cancer cells by interferon-alpha

Continuous exposure of human breast cancer cells, MCF-7, to interferon-alpha (IFN) induces a state.of non-responsiveness termed as desensitization. mRNA 561 is transiently induced by IFN-alpha in MCF-7 cells, peak cytoplasmic levels are reached by six to twelve hours; the mRNA level declines steadily and is reduced to uninduced levels by forty eight hours. Induction of mRNA 561 was used as an index of responsiveness of cells to IFN-alpha and desensitization was characterized in MCF-7 cells and in MCF-7 cells transfected by the v-H-ras oncogene (MCF-7ras). The kinetics and degree of IFN-mediated induction of mRNA 561 was comparable in both the cell lines. Desensitization was observed in MCF-7 cells and not in MCF-7ras. It was a reversible event, requiring de novo protein synthesis as inclusion of cycloheximide inhibited desensitization. The cellular elements that mediate such a phenomena are elicited by IFNs during the initial phases of IFN action and may be polypeptides. The refractory period, the time after which MCF-7 cells become responsive, was determined to be five days. In conclusion, we demonstrate the use of mRNA 561 induction in evaluating desensitization. Inhibition of protein synthesis or transfection with ras blocks desensitization in MCF-7 cells.     

Effects of L-ascorbic acid supplementation on dieldrin toxicity in rats

Chronic dieldrin administration to rats (5 mg/kg/day) produced pathological changes in liver and kidney tissues. Dieldrin treated rats showed high levels of liver ascorbic acid and increased activities of inorganic pyrophosphatase in brain and glucose-6-phosphatase in liver. The activities of Mg²⁺-ATPase in liver and acetylcholinesterase in brain were decreased under toxic doses of dieldrin. L-Ascorbic acid supplements in treated animals could partially prevent the pathological alterations, as observed histologically in liver and kidney tissues. Administration of this vitamin could also prevent alterations in some enzyme activities produced by toxic dieldrin doses.     

Study of lymphatic metastatic patterns in gastric carcinoma according to tumor location

A total of 226 cases of advanced gastric cancer which occupied only one third of the stomach were analyzed in order to clarify whether and how lymphatic spread differed according to the tumor location and gross type of tumor. Out of the 226 patients, 45 cases had tumor in the upper third, 74 cases had it in the middle third, and 107 cases had it in the lower third of the stomach. The incidence of lymph node metastasis was found to be much higher for the tumors located in the lesser curvature (51.6%), greater curvature and posterior wall (54.4%), as compared to the tumors located in the anterior wall (28.0%). The tumors located in the upper third of the stomach did not show any metastasis in the N3 node, while the tumors located in the lower third of the stomach did not show any metastasis in the left cardial nodes, short gastric nodes, and the nodes along the left gastroepiploic vessels. Similarly, the tumors from the middle third of the stomach did not invade the left cardial nodes.     

Identification of a novel pulmonary oedema producing toxin from Indian red scorpion (Mesobuthus tamulus) venom.

The experiments were conducted to identify the toxin that produces pulmonary oedema in Mesobuthus tamulus (BT) envenomed animals. Crude BT venom was subjected to Sephadex gel filtration (G-75) and the fractions were screened for optical density (OD), neurotoxicity (prolongation of compound action potential in frog sciatic nerve) and lethality. All these parameters exhibited a peak between 54-94 ml eluates. Fractions of this peak were pooled (SP) and loaded on to carboxymethyl cellulose column. The column was then eluted with increasing buffer concentrations at constant pH and temperature. Eluates were screened for neurotoxicity and OD. Four peaks of neurotoxic activity (T1-T4) were detected. T2 and T3 were lethal whereas T1 and T4 were non-lethal. T2 exhibited mainly neurotoxicity and failed to augment phenyldiguanide (PDG)-induced reflex response or to produce pulmonary oedema. T3 was having minimal neurotoxic actions but augmented PDG-reflex and produced pulmonary oedema. The effects of T3 persisted even after dialysis with 8 kDa cut-off filter but not those of T2. The T3 effects resembled toxic manifestations of BT venom and were blocked by aprotinin pre-treatment. T3 demonstrated a band at approximately 100 kDa in SDS-PAGE. The results demonstrate the presence of a lethal, high molecular weight, pulmonary oedema producing toxin in BT venom.