Cisplatin-induced reductions in renal functional reserve uncovered by unilateral nephrectomy: an experimental study in the pig

Summary Groups of mature Large White female pigs, approximately 10 months of age, received single intravenous infusions of 1.5, 2 or 2.5 mg/kg body weight (equivalent to90, 120 and 150 mg/m²) cisplatin. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured before and at 4 weeks after cisplatin infusion by renography using [^{99 m}Tc]-DTPA (diethylenetriamminepentaacetic acid and iodohippurate sodium I 131, respectively. The left kidney of each cisplatin-treated animal plus that of four age-matched control pigs was then removed surgically,and GRF and ERPF were measured in the remaining kidney at 4 weekly intervals for up to 24 weeks after unilateral nephrectomy (UN). The pigs treated with cisplatin exhibited no consistent change in either GFR or ERPF at 4 weeks after treatment. A histological evaluation of kidneys from animals treated with 2mg/kg cisplatin that had been removed at UN revealed both tubular and glomerular lesions. The latter consisted of cell proliferation on the parietal surface of the urinary space; damage to the S₁ portion of the proximal convolution was also noted. Following UN there was a pronounced dose-dependent reduction in the functional status of the remaining kidney such that the increase in GRF and ERPF in pigs initially receiving 2.5 mg/kg cisplatin was <50% of that seen in age-matched UN controls. Moreover, the glomerular lesions observed at 4 weeks after cisplatin infusion had apparently progressed to glomerular hyalinisation by 24 weeks after UN. Thus, prior treatment with cisplatin may cause a permanent reduction in renal functional reserve that may be clinically silent until exposure to an additional nephrotoxic insult.This study was supported by the Cancer Research Campaign     

Monkeypox outbreak 2022: What we know so far and its potential drug targets and management strategies

Monkeypox is a rare zoonotic disease caused by infection with the monkeypox virus. The disease can result in flu-like symptoms, fever, and a persistent rash. The disease is currently spreading throughout the world and prevention and treatment efforts are being intensified. Although there is no treatment that has been specifically approved for monkeypox virus infection, infected patients may benefit from using certain antiviral medications that are typically prescribed for the treatment of smallpox. The drugs are tecovirimat, brincidofovir, and cidofovir, all of which are currently in short supply due to the spread of the monkeypox virus. Resistance is also a concern, as widespread replication of the monkeypox virus can lead to mutations that produce monkeypox viruses that are resistant to the currently available treatments. This article discusses monkeypox disease, potential drug targets, and management strategies to overcome monkeypox disease. With the discovery of new drugs, it is hoped that the problem of insufficient drugs will be resolved, and it is not anticipated that drug resistance will become a major issue in the near future.     

Zur Epidemiologie depressiver Störungen im Alter

In this essay national and international psychiatric-epidemiological studies on the subject of “depressive disorders in the elderly” are discussed. Although empirical case finding studies focused on in the essay have difficult problems to contend with, the attempt is made to systematize the prevalence and incidence rates of depressive disorders in the elderly population. The second part (publication in magazine 2/97) deals with the epidemiology of depressive disorders for the elderly. This article will present prevalence and incidence rates of depressive disorders in general and their depressive subtypes.     

Severe malaria in African adults living in a seasonal endemic area

Objective This study investigates severe malaria in african adults living in a seasonal endemic area.Design: A prospective study of all adults admitted with severe malaria over 2 consecutive seasons: October 1990 till January 1991 and October 1991 till January 1992.Setting ICU (15 beds) of Hôpital Principal, Dakar, Sénégal.Patients 23 patients: 14 men and 9 women with a mean age of 30±3 years were included in the study; all fulfilled the 1990 WHO criteria for severe malaria.Results At admission, 12 patients were comatose (Glasgow Coma Scale<10), 7 had generalized convulsions. Parasitaemia was 135±52×10⁹/l. Biological indications of severity were as follows: hypophosphataemia <0.8 mmol/l in 14 cases, serum creatine phosphokinase >500 IU/l in 15 cases; and PaO₂<70 mmHg in 5 cases. Serum TNF levels, measured in 16 cases, were increased at 298.4±63.5 pg/ml, serum levels of IL-6 and IL-2SR were also elevated: 609.5±304.2 pg/ml and 297.6±35.6 pg/ml respectively. Circulating IgM and IgG antibodies were found in 14 out of 16 patients. Serum levels of TNF, IL-6 and IL-2SR correlated positively with each other. TNF and IL-2SR were also positively correlated to parasitaemia. Intravenous therapy with quinine at loading dose was favorable in 19 patients. Four patients died during the study, 3 from multiple organ failure.Conclusions: This work demonstrated that severe malaria in a seasonal endemic area displays original clinical features with a high rate of either cerebral malaria or multiple organ failure.     

Bone island (enostosis): current concept — a review

An enostosis or bone island represents a focus of mature compact (cortical) bone within the cancellous bone (spongiosa). Thought by some to be a tumor-like condition and by others a hamartoma, this benign lesion is probably congenital or developmental in origin and reflects failure of resorption during endochondral ossification. A bone island can be virtually diagnosed based on its characteristic clinical and radiologic features. Typically asymptomatic, the lesion is usually an incidental finding, with a preference for the pelvis, femur, and other long bones, although it may be found anywhere in the skeleton, including the spine. Plain radiography reveals a homogeneously dense, sclerotic focus in the cancellous bone with distinctive radiating bony streaks (thorny radiation) that blend with the trabeculae of the host bone, creating a feathered or brush-like border. On CT scan, a bone island appears as a low-attenuation focus, and on MRI sequences it shows low signal intensity like cortical bone. A distinguishing feature of bone islands is that they are usually cold on skeletal scintigraphy. Thus, bone scan has been and continues to be the means of differentiating bone islands from the more aggressive entities. However, reports of histologically confirmed bone islands that were scintigraphically active have raised a note of caution about relying on this modality in the differential consideration of lesions otherwise characteristic of bone islands. Guides to the correct diagnosis should be looked for in the individual clinical situation and in the morphologic features of the lesion on plain radiography, CT, and MRI, without regard to the lesion's activity on bone scan. If such a lesion, however, is symptomatic and hot on scintigraphy, it demands close observation with follow-up imaging studies.     

A Guide to Immunotherapy of Genital Warts

Genital warts affect at least 1% of sexually active adults. Current therapies are inadequate because they are often painful, may fail to prevent recurrence and transmission of warts, and usually require either surgery or at least application by a physician. Investigation of immunotherapy for genital warts began with interferon. It has been studied in topical, intralesional, systemic and adjuvant applications. We review the major clinical trials of interferon for genital warts, and conclude that intralesional therapy with interferon-alpha or interferon-beta, with complete response rates of 36 to 63%, is the most successful route for interferon monotherapy. In choosing patients for therapy with interferon, major considerations include immune status, pregnancy and ability to return for frequent injections. Imiquimod is a new immune response enhancer that acts through stimulating host cytokine production. Interleukins-1, -2, -6, -8 and -12, interferons alpha, beta and gamma and tumour necrosis factor alpha have all been associated with the mechanism of action of imiquimod. Recently, 3 clinical trials have reported positive results using topical imiquimod to treat genital warts. Complete response rates ranged from 37 to 54% for these controlled trials of 5% imiquimod cream. Adverse effects reported include localised pruritis, erythema, erosion, burning and pain, which were rarely severe enough to cause discontinuation of the medication. Although further trials are necessary to identify the role of imiquimod in the therapy of genital warts, it appears to be an efficacious and well tolerated patient-controlled measure for wart therapy.