Oral Mucositis: Time for More Studies

Oral Mucositis (OM) is a frequent cause of severe morbidity in patients receiving chemotherapy and/or radiotherapy. The pathophysiology of OM involves direct cytotoxic effects, local inflammatory responses, and alterations in oral microflora. There are currently no approved agents for the prevention or treatment of OM. In this review we briefly describe current knowledge of the pathophysiology, clinical presentation, and management of OM. We then discuss investigational agents being studied in OM with a particular focus on local antimicrobial agents, hemopoietic growth factors, and cytokines. Measures to reduce the incidence of OM and/or alleviate its clinical sequelae should be incorporated into all chemotherapy or radiotherapy studies.     

The African Programme for Onchocerciasis Control: impact on onchocercal skin disease

Objectives To assess the long‐term impact of the African Programme for Onchocerciasis Control on itching and onchocercal skin disease (OSD). Methods Seven study sites in Cameroon, Sudan, Nigeria and Uganda participated. Two cross‐sectional surveys were conducted of communities meso‐ and hyper‐endemic for onchocerciasis before and after 5 or 6 years of community‐directed treatment with ivermectin (CDTI). Individuals were asked about any general health symptoms including itching and underwent full cutaneous examinations. Onchocercal skin lesions were documented according to a standard classification. Results Five thousand one hundred and ninety three people were examined in phase I and 5,180 people in phase II. The presence of onchocercal nodules was a strongly significant (P < 0·001) risk factor for all forms of onchocercal skin disease: APOD (OR 1·66); CPOD (OR 2·84); LOD (OR 2·68); reactive skin lesions (OR 2·38) and depigmentation (OR 3·36). The effect of community‐directed treatment with ivermectin was profound. At phase II, there were significant (P < 0·001) reductions in the odds of itching (OR 0·32), APOD (OR 0·28); CPOD (OR 0·34); reactive skin lesions (OR 0·33); depigmentation (OR 0·31) and nodules (OR 0·37). Reduction in the odds of LOD was also significant (OR 0.54, P < 0.03). Conclusions This first multi‐country report of the long‐term impact of CDTI reveals a substantial reduction in itching and OSD. APOC operations are having a major effect in improving skin health in poor rural populations in Africa.     

Peripheral Neuropathy as a Presenting Feature of Type 2 Diabetes: A Case-Controlled Study

The characteristics and outcome of 68 newly diagnosed Type 2 diabetic patients who presented with clinically evident peripheral neuropathy were compared with matched controls who had no neuropathy at diagnosis. All subjects (34 male) whose median age was 68 (range 47–89) yr were identified from a computerized diabetes register and presented in 1982–1990. The groups were compared at diagnosis for haemoglobin A₁, body mass index, blood pressure, smoking, and alcohol consumption, and for co-existent coronary and peripheral vascular disease. Mortality and morbidity were recorded to March 1991. Significantly more patients with neuropathy had co-existent peripheral vascular disease: 24(35%) compared to 6(9%) controls (p = 0.0021). Twenty (30%) of those with neuropathy and no controls had retinopathy at diagnosis, which was sight-threatening in 10. Seven (10%) with neuropathy but no controls presented with foot ulcers, one requiring limited amputation. Two more patients with neuropathy and one control subsequently developed foot ulcers resulting in one or more amputation in each group. Twenty-one (31%) of those with neuropathy and 14 (21%) controls died (p = 0.2109). In conclusion more diabetic patients with clinically evident peripheral neuropathy at diagnosis have peripheral vascular disease than matched patients without neuropathy. It is likely that macrovascular disease either exacerbates or causes the neuropathy in this group of patients. They are at high risk of developing foot ulceration and high priority should be given to foot care in planning their management.     

Epilepsy: A Clinical Overview

The diagnosis and treatment of seizures and epilepsy is a common task of the physician. Approximately 1 in 10 people will have a seizure during their lifetime. Epilepsy is the tendency to have unprovoked seizures. Epilepsy is the fourth most common neurological disorder and affects 1 in 26 people in the United States and 65 million people worldwide. Evaluation of a patient presenting with a seizure involves excluding an underlying neurologic or medical condition, classifying the seizure type and determining if the patient has epilepsy. Proper treatment requires accurate diagnosis of the epilepsy type and syndrome and use of a medication that is effective and without adverse effects. Most patients can achieve complete seizure control with medication, but if medication is unsuccessful, surgical treatment can be an option. Special situations in the care of people with epilepsy include status epilepticus, women with epilepsy, the older adult, and safety issues.     

Continuously Nebulized Albuterol in Severe Exacerbations of Asthma in Adults: A Case-Controlled Study

A retrospective, case-controlled analysis comparing patients admitted to a medical intensive care unit with severe exacerbations of asthma who received continuously nebulized albuterol (CNA) versus intermittent albuterol (INA) treatments is reported. Forty matched pairs of patients with asthma are compared. CNA was administered for a mean of 11 ± 10 hr. The incidence of cardiac dysrhthmias was similar between groups. Symptomatic hypokalemia did not occur. CNA patients had higher heart rates during treatment, which may reflect severity of illness. The incidence of intubation was similar. We conclude that CNA and INA demonstrated similar profiles with regard to safety, morbidity, and mortality.     

Continuously Nebulized Albuterol in Severe Exacerbations of Asthma in Adults: A Case-Controlled Study

A retrospective, case-controlled analysis comparing patients admitted to a medical intensive care unit with severe exacerbations of asthma who received continuously nebulized albuterol (CNA) versus intermittent albuterol (INA) treatments is reported. Forty matched pairs of patients with asthma are compared. CNA was administered for a mean of 11 ± 10 hr. The incidence of cardiac dysrhthmias was similar between groups. Symptomatic hypokalemia did not occur. CNA patients had higher heart rates during treatment, which may reflect severity of illness. The incidence of intubation was similar. We conclude that CNA and INA demonstrated similar profiles with regard to safety, morbidity, and mortality.     

Stem Cell Therapy Trials: A Call for Standardization

There are currently 25 new clinical cellular therapy trials in progress for cardiovascular disease in the US, and a similar number ongoing in Europe. The lack of standardization in cell isolation, preparation, storage, and time and localization of delivery, present clear hurdles to this growing field. This emphasizes the need for an organized task force to work closely with the FDA to agree upon standardized methods with the end result being improvements in patient care and enhanced knowledge in the field.     

Onchocerciasis in southwestern Sudan: parasitological and clinical characteristics

Parasitological and clinical observations were made on residents of Pongo Nuer, a village in the province of Bahr El Ghazal, southwestern Sudan. Of 202 skin biopsies, 189 (94%) were positive for microfilariae of Onchocerca volvulus. Nodules were most common around the pelvic girdle and rare on the limbs or head. Microfilarial intensities, ranging up to 1,094 mf/mg of skin, were highest at the iliac crest and shoulder; they increased rapidly in childhood but then appeared to reach a plateau maintained through adult life. Nodule presence and number, especially at multiple sites, was significantly related to skin microfilarial intensity. Dermal manifestations of O. volvulus infection were widespread and severe, ranging from acute maculopapular eruptions to chronic, diffuse, and degenerative changes, even in young adults. However, high skin microfilarial intensities were found in asymptomatic individuals; conversely, lowest intensities were in those with severest maculopapular lesions, suggesting that host response was a major determinant of disease outcome. Microfilariae were detected in the cornea or anterior chamber of the eyes of one third of those examined in all age groups, but lesions of the posterior segment, including optic neuritis, chorioretinitis, and pigmentary abnormalities, were considered responsible for visual deficits in the population sample. Some pathologic changes in the anterior segment attributable to microfilariae were more common in the young than in adults but there was no preponderance of sclerosing keratitis in adults, contrary to expectations in hyperexposed individuals in a Sudan savannah zone. The best correlate of the presence of microfilariae in the eye was the intensity of infection in shoulder skin snips. Little value could be derived from data on outer canthus samples, either in terms of severity of ocular infection or disease. Microfilaremia was common (76%) but in only one case was attributed to O. volvulus; the remainder were due to Mansonella perstans.     

In Vitro and In Vivo Studies on Filter Collected Granulocytes

The in vitro function of granulocytes collected by filtration leukapheresis after premedication of donors with dexamethasone was found to be normal. In vivo studies were performed in a 21-year-old woman who was transplanted with allogeneic bone marrow for severe aplastic anaemia. The patient received granulocyte transfusions for treatment of septicaemia during the transplantation period. On 11 consecutive days an average dose of 7.2 times 10¹⁰ granulocytes/ d was given. Under this therapy remission of fever occurred. On d 6 after bone marrow transplantation, the patient died from cardiac failure. Transfused granulocytes were found ante mortem in a pericardial effusion and post mortem in lungs, kidneys, liver and spleen. The data indicate that filter collected granulocytes function normally in the recipient and are clinically effective.     

In Vitro Studies on Erythrophagocytosis

1. Two systems for the quantitative study of erythrophagocytosis in vitroare described.

2. The effects of a number of physical factors, cations, anticoagulants, andmetabolic poisons in these systems are reported.

3. Existing views on the mechanism of action of factors influencing phagocytosis are briefly reviewed. The importance of the state of energy metabolismof the phagocyte is stressed.

4. The importance of physical, chemical, and metabolic aspects of erythrophagocytic systems is emphasized in connection with the use of erythrophagocytosis as a serologic tool in immunohematology.

Submitted on January 15, 1963 Accepted on May 16, 1963     

Effects of Ethanol on Rat Sertoli Cell Function: Studies In Vitro and In Vivo

Chronic alcohol administration to male animals is associated with testicular atrophy and gonadal failure. The Sertoli cell seems to be the first testicular cell injured as a result of alcohol exposure. To investigate the adverse effects of ethanol on testicular and particularly Sertoli cell function, the consequences of in vivo and in vitro ethanol exposure on rat Sertoli cell mRNA and protein levels of transferrin and ornithine decarboxylase were investigated. In vivo, ethanol exposure enhanced the levels of both hepatic and testicular (Sertoli cell) transferrin protein and mRNA. Ethanol exposure also enhanced testicular, but not hepatic, levels of ornithine decarboxylase protein and mRNA. These in vivo findings were confirmed when isolated Sertoli cells were studied in vitro. Specifically, ethanol exposure increased Sertoli cell transferrin protein and mRNA levels. Ethanol exposure increased Sertoli cell ornithine decarboxylase mRNA and protein when cultured in serum-free media, but not when cultured in the presence of serum. These studies demonstrate that ethanol exposure of rat Sertoli cells is associated with alterations in the levels of mRNA and protein that are known to be important in the process of spermatogenesis. These findings add to the body of evidence that suggests that, within the testes, the Sertoli cell may be an important target for ethanol-induced gonadal injury.