INTERFERONS IN ONCOLOGY

SUMMARY The interferons are natural glycoproteins secreted in response to various stimuli, including viral infection. They have antiviral, antiproliferative and immunomodulatory effects on different target cell populations. Since recombinant human interferons have become available, they have been tested in a wide range of malignancies. They are well established in the treatment of hairy cell leukaemia, chronic myelogenous leukaemia and multiple myeloma. Although they have documented activity against lymphoma, melanoma, renal cell cancer and carcinoid tumours, their role in the treatment of these tumours is less clear. In the common solid tumours, such as lung cancer and colorectal cancer, the use of interferons remains experimental. Here we will summarise their practice applications in oncology, using randomised studies where available to establish their place in multi-modality treatment. We will not discuss their use as antiviral or immunomodulating agents in viral and autoimmune diseases, multiple sclerosis or after organ transplantation.     

An audit of bronchoscopy practice in the United Kingdom: a survey of adherence to national guidelines

BACKGROUND: Both patient and staff safety are of major importance during the procedure of fibreoptic bronchoscopy. Patient safety depends partly on adequate disinfection of instruments and accessories used as well as careful monitoring during the procedure. Adequate facilities, manpower and training are also essential. Staff safety depends partly on adequate procedures to minimise any risks of sensitisation to agents such as glutaraldehyde. An audit was carried out of bronchoscopy procedures in hospitals in the UK and the findings were compared with published guidelines on good practice and clinical consensus. METHODS: A postal questionnaire was sent to 218 bronchoscopy units in the UK. Findings were then compared with published evidence of good practice in the areas of disinfection, including the use of glutaraldehyde, patient monitoring, manpower, facilities, and training. RESULTS: A 73% response rate was obtained. Recommended minimum disinfection times before and after routine bronchoscopies were not achieved by 35% of units. No disinfection was carried out in 34% of units before emergency bronchoscopies and in 19% of units after suspected cases of tuberculosis. Adequate rinsing of the bronchoscope with sterile or filtered water was not carried out by 43% of units. Contrary to recommendations, 31% of departments were still using glutaraldehyde in the patient examination room and inadequate room ventilation was common. Protective clothing was often not worn by staff during bronchoscopy. Inadequate intravenous access and use of supplementary oxygen were found in many units. Practice standards were higher in departments where dedicated bronchoscopy/endoscopy units of the hospital were used, and also where staff had been on external training courses. CONCLUSIONS: This audit has shown that many units do not adhere to guidelines on disinfection procedures and patient monitoring. Unnecessary potential risks due to staff exposure to glutaraldehyde were apparent. National guidelines on good practice are not being followed in areas which may potentially affect patient and staff safety.


     

Low HIV-1 proviral DNA burden detected by negative polymerase chain reaction in seropositive individuals correlates with slower disease progression.

During 1989, 316 members of a cohort of homosexual men were tested for HIV-specific DNA by the polymerase chain reaction (PCR) using a pair of gag-region primers. Of 125 HIV-seronegative subjects, 123 (98.4%) were PCR-negative while 158 (82.7%) of 191 HIV-seropositive subjects were PCR-positive. Fewer of the 33 subjects who were seropositive and PCR-negative were at Centers for Disease Control (CDC) stage IV than the seropositive, PCR-positive subjects (6 versus 25%; P = 0.030). The seropositive, PCR-negative group had higher mean CD4 counts (640 versus 490 x 10(6) cells/l; P = 0.006), higher CD4: CD8 ratios (0.92 versus 0.64; P = 0.004), lower immunoglobulin (Ig) G levels (1290 versus 1645 mg/dl; P = 0.002), lower IgA levels (168 versus 251 mg/dl; P less than 0.001), and lower C1q binding activity (8 versus 14%; P = 0.010) than the seropositive, PCR-positive subjects. The median rate of CD4 cell decline in the 3 years preceding the PCR sample was less marked in the seropositive, PCR-negative group than the seropositive, PCR-positive group (-58 versus -77 x 10(6) cells/l per year; P = 0.028). To control for duration of infection, we restricted the analysis to the subgroups of 11 seropositive, PCR-negative subjects and 34 seropositive, PCR-positive subjects who had seroconverted earlier in the cohort study. Both subgroups had similar durations of infection, yet the same pattern of differences persisted.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical relevance of histologic subtyping in small cell lung cancer

Histopathologic specimens from 249 patients with small cell lung cancer (SCLC) were reviewed and classified into oat cell-type, pure intermediate cell-type (excluding specimens with mixed small cell/large cell features), and small cell/large cell-type. One hundred seventy (68%) specimens displayed oat cell features (including 30 with mixed oat cell/intermediate cell features), 66 (27%) displayed intermediate cell features, and 13 (5%) displayed mixed small cell/large cell features. No differences among these subtypes were found with respect to stage of disease, sex, age, performance status, and number and distribution of metastases. Complete and partial remission rates for the oat cell-type were, respectively, 31% and 38%, for the intermediate cell-type 20% and 45%, and for the small cell/large cell-type 38% and 31%. Two-year survival rates were 7%, 11%, and 15%, respectively. These data were all statistically insignificant, and comparisons of log-rank analyses of survival curves for these SCLC subtypes also showed no statistically significant differences. We thus conclude that histologic subtypes of SCLC are not distinct entities of clinical relevance, and that prognostic as well as therapeutic decisions cannot be based on histologic subtyping.     

Immunologische Toleranz nach experimenteller Lebertransplantation

Zusammenfassung Im Vergleich zu anderen primär vaskularisieren Organtransplantaten in der Ratte werden Lebertransplantate schwächer abgestoßen, besitzen eine bessere Überlebensrate und können in bestimmten Spender-Empfänger-Kombinationen eine spenderspezifische Hyporeaktivität oder Toleranz induzieren. In dieser Übersicht werden die immunologischen Mechanismen dieses privilegierten Status beleuchtet. Eine Vielzahl möglicher Mechanismen, wie die Generation von Suppressor-T-Zellen, humorale Faktoren und Mikrochimärismus, sind mit der beobachteten Hyporeaktivität in Verbindung gebracht worden. Eine weitere Analyse dieser Phänomene könnte zur Entwicklung von Protokollen für die klinische Organ-transplantation beitragen, die zur Etablierung einer spenderspezifischen Hyporeaktivität ohne die Notwendigkeit einer lebenslangen Immunsuppression führen.

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Immunologic tolerance following liver transplantation

Allografts in the rat liver are rejected less vigorously than other primarily vascularized allografts; they show a better survival rate and induce donor-specific unresponsiveness or tolerance in some donor-recipient combinations. This overview focuses on the immunologic mechanisms of this privileged status of liver allografts. A variety of possible mechanisms, such as generation of suppressor T-cells, humoral factors and microchimerism, has been related to the observed hyporeactivity. A further analysis of these phenomena may enhance the development of clinical organ transplantation protocols that allow for establishment of donor-specific unresponsiveness without the need for life-long immunosuppression.

     

Low viscosity histidine-tryptophan-ketoglutarate graft flush improves subsequent extended cold storage in University of Wisconsin solution in an extracorporeal rat liver perfusion and rat liver transplantation model.

Adequate flushing for liver donation requires large fluid volumes delivered at a high flow. This can be achieved more effectively with crystalloid solutions than with colloid-based solutions. This study examined the combination of initial histidine-tryptophan-ketoglutarate solution (HTK) graft flush and subsequent storage in University of Wisconsin solution (UW) to that of the single use of each solution. Livers from inbred Wistar rats were procured using aortic perfusion with UW or HTK for initial perfusion and reflushed after 30 minutes using either solution. In a third group, after perfusion with HTK, organs were reflushed with UW. A 60-minute in-vitro recirculating perfusion was performed after 24 hours of cold storage in the subsequent solution, as well as allotransplantation after 18 and 24 hours of cold storage. In extracorporeal perfusion, the HTK flush followed by UW storage was superior compared to the single use of either UW or HTK solution, as measured by portal venous pressure, bile flow, liver enzymes released into the effluent perfusate, glycerol leakage, and histological examinations. These data were consistent with the transplantation study. Histological damage and enzyme release after 5-day survival were lowest in the HTK flush and subsequent UW storage groups following 18 hours of cold storage; likewise, the 5-day survival was superior following 24 hours of cold storage. In conclusion, the combined use of HTK solution for initial graft rinse and subsequent storage in UW solution resulted in a cumulative protection. Choosing low-viscosity HTK solution for the initial organ flush may represent a feasible improvement in liver preservation, which also further reduces the required amount of UW solution.