Assessing ototoxicity and patients' satisfaction of topical local anaesthesia in myringotomy and ventilation tube insertion.

OBJECTIVES: Animal studies have suggested that exposure of the middle ear to topical local anaesthesia may be ototoxic. This study aimed to report sensorineural hearing outcomes and patients' satisfaction in those who underwent myringotomy and ventilation tube insertion using topical local anaesthesia. METHODS: Twenty-nine patients (32 ears) were operated on. Pre- and post-operative audiology findings were compared. A Likert-type questionnaire on treatment satisfaction was completed at the end of the procedure. RESULTS: Median patient age was 55 years (range, 27-88 years). Pre- and post-operative bone conduction pure tone averages were 26.76 dB and 25.26 dB respectively (mean reduction of -1.22 dB, 95 per cent confidence interval of -5.91 to 8.13 dB; p = 0.7538). One ear (3 per cent) had a reduction in pure tone average of 10 dB. CONCLUSION: The results suggest that sensorineural hearing loss is not a complication of ear exposure to topical local anaesthesia during myringotomy and ventilation tube insertion. The procedure was well perceived.

RICKETS IN RURAL KENYAN PRESCHOOL CHILDREN: CASE REPORT.

Clinical rickets has not been reported previously in Embu district, Kenya. Baseline clinical assessments performed for a nutrition intervention study in preschool children (n=324) identified 28 cases of rickets (8.6% of study sample). Clinical characteristics included: delays of sitting, walking, and teething; bone and chest deformities; widened wrists and ankles; and bowed lower extremities. Risk factors identified were short duration of breastfeeding with feeding of cereal-based supplements with little or no milk, low calcium intake, limited sunlight exposure. Vitamin D and calcium deficiencies likely contributed to these cases. Treatment with Vitamin D3 and milk resulted in clinical improvement.

Involvement of adrenoceptors in the angiotensin II-induced expression of inducible transcription factors in the rat forebrain and hypothalamus.

Angiotensin II (Ang II) acts as a neuromodulator/neurotransmitter in specific brain nuclei involved in the regulation of blood pressure and volume homeostasis. It also induces a highly differentiated transcription factor expression in these nuclei. We investigated whether adrenoceptors, which modulate other central actions of angiotensin II like the vasopressin release, also play a role in the AT1 receptor-mediated expression of the transcription factors (TF) c-Fos, c-Jun and Krox-24 in the rat brain. Ang II, injected intracerebroventricularly, induced the expression of c-Fos, c-Jun and Krox-24 in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Pretreatment with the alpha 1-adrenoceptor antagonist, prazosin, significantly inhibited the Ang II-induced transcription factor expression in the SON and PVN. The alpha 2-adrenoceptor antagonist, yohimbine, also reduced Ang II-stimulated transcription factors significantly in both nuclei. This inhibition was mainly localized in vasopressinergic magnocellular neurons in both nuclei. The beta-adrenoceptor antagonist, propranolol, did not influence the Ang II-induced expression of TF. Our results show that both, Ang II-induced vasopressin release and transcription factor expression, involve the same neuronal connections in the brain, implicating that the signal transduction pathways leading to the two different effects are at least to a certain degree convergent.

Multidisciplinary symptom control clinic in a cancer center: a retrospective study.

Our objective in this study was to review the characteristics, symptom intensity and satisfaction of patients referred to a half-day symptom control clinic (SCC) for advanced cancer patients. This was a retrospective study. The setting was a multidisciplinary symptom control clinic in a cancer centre. Those taking part were 166 consecutive advanced cancer patients referred to the half-day multidisciplinary SCC because of symptom distress. Patients referred to the clinic were assessed in a private room by a physician, a nurse, a pharmacist, a psychologist, and social, rehabilitation, nutrition, respiratory and pastoral care workers. Symptom distress (multiple visual analogue scales), cognition, and CAGE (alcoholism) were determined. Recommendations were given to the patient and sent to the oncologist, family physician and home care nurse. For 110 patients a second assessment was carried out 1 week later, and 64 patients underwent a telephone assessment 2 weeks after the second visit. Symptom intensity was determined during initial and follow-up visits, as well as during two follow-up telephone assessments. In addition, demographics and patient satisfaction with the SCC were determined. Overall symptom distress, depression, anxiety and sensation of wellbeing improved significantly from the first (n = 166) to the second clinic visit (n = 110). Further significant improvement was observed in overall symptom distress, pain, anxiety, sense of wellbeing and depression at the 2- (n = 64) and 4-week (n = 38) telephone follow-up assessments. Mean satisfaction with the SCC (0-10) was 7.7 +/- 2. Our findings suggest that the work of the SCC results in long-term effectiveness in symptom control and high levels of patient satisfaction. The SCC allows for better integration of care between a cancer center and community-based physicians and nurses. It also allows patients access to multiple disciplines that are not available outside tertiary centers.

Graft-versus-host disease-like immunophenotype and apoptotic keratinocyte death in paraneoplastic pemphigus.

Paraneoplastic pemphigus (PP) is an autoimmune disease, which is frequently associated with non-Hodgkin's lymphoma. Autoantibodies against components of the cytoplasmic plaque of epithelial desmosomes are usually present in the sera and are believed to play a major pathogenic part in acantholysis and suprabasal epidermal blistering. However, another typical histological feature of PP, interface dermatitis with keratinocyte dyskeratosis, is shared with skin diseases that involve epithelial damage mediated by T cells. Here, we present the detailed characterization of the cutaneous T-cell response in a patient with PP and demonstrate a selective epidermal accumulation of activated CD8+ T cells together with an increased local production of interferon-gamma and tumour necrosis factor-alpha, and a strong expression of HLA-DR and ICAM-1 on keratinocytes. Apoptosis was identified as a key mechanism of keratinocyte death, and appeared independent of the FAS/FAS ligand (FAS-L) pathway, as epidermal expression of FAS was not increased compared with normal skin, and FAS-L was undetectable on the protein and mRNA level. Triple therapy with high-dose corticosteroids, cyclophosphamide and intravenous immunoglobulins reduced levels of pemphigus-like autoantibodies and reversed the cutaneous inflammatory reaction leading to long-standing clinical remission. Our findings support the concept of a major contribution of cytotoxic T lymphocytes to the immunopathology of paraneoplastic pemphigus.

Achieving success: assessing the role of and building a business case for technology in healthcare.

As the healthcare market continues to evolve, technology will play an increasingly important role in an integrated delivery system's ability to provide high-quality, cost-effective care. Healthcare leaders must be proactive and forward thinking about their technology investments. The financial investment for technology innovation can be significant. Therefore, it is important that healthcare executives deliberately design the role of technology and develop a consistent method for evaluating, identifying, and prioritizing technology investments. The article begins by describing technology's role in a healthcare organization as a window to the organization, a key driver of business strategy, and a high-performance enabler, and it develops a seven-step process for building a business case to ensure that an organization's technology investments are wise, well-reasoned, and will provide value to its customers. In addition, the article discusses the importance of combining people and process reengineering with new technology to exponentially increase the value to an organization. Healthcare leaders must understand the multiple roles of technology and consistently develop a business case when making technology investment decisions. Organizations driven by such an understanding will have a robust infrastructure of enabling technology designed to integrate people and process elements with technology to achieve the goals and initiatives of the organization. These organizations will lead the healthcare industry into the next millennium.

PROTECT interim results: a large multicenter study of patients with type II diabetes. Precose Resolution of Optimal Titration to Enhance Current Therapies.

The Precose Resolution of Optimal Titration to Enhance Current Therapies (PROTECT) study is an ongoing Phase IV clinical trial designed to assess the effectiveness, tolerability, and safety of acarbose tablets in patients with type II diabetes when the dosage is slowly titrated upward. This multicenter, open-label, 28-week trial will enroll approximately 7,000 type II diabetic patients. The present report describes the interim results for 2,139 patients who completed the trial as of November 1, 1996. Patients with type II diabetes enrolled in the study were inadequately controlled either with diet alone or with a sulfonylurea. The dosage of acarbose was titrated from 25 mg three times a day (TID) to 100 mg TID based on tolerability and efficacy. Efficacy of glycemic control was assessed by changes in glycated hemoglobin A1c (Hb A1c) and 1-hour postprandial plasma glucose (PPG) levels. Tolerability and safety were determined by patient reports of treatment-emergent adverse events and by review of laboratory tests. The PROTECT study confirms the previously demonstrated efficacy and safety of acarbose in improving glycemic control in patients with type II diabetes regardless of a patient's age, body weight, ethnic background, time since diagnosis, or severity of disease. mean 1-hour PPG levels declined throughout the entire treatment period, with a mean decrease from baseline of -47 mg/dL at the end of treatment. Hb A1c, the most reliable indicator of long-term glycemic control, decreased over the course of treatment, resulting in a mean decrease of -0.7% (P < 0.001). Although all patient types enrolled in the study responded positively to therapy, certain subgroups responded particularly well, such as those patients diagnosed with the disease less than 1 year ago, those treated with acarbose as monotherapy, and those with higher baseline Hb A1c levels. Adverse events were experienced by 36% of all patients and consisted primarily of gastrointestinal disturbances (flatulence, diarrhea, abdominal pain). Moderate renal insufficiency (serum creatinine levels between 1.5 and 2 mg/dL) was present in 259 patients, and no patients developed serum hepatic transaminase levels more than twice the normal range.

The sweat of patients with atopic dermatitis contains specific IgE antibodies to inhalant allergens.

We have investigated levels of total and specific IgE against inhalant allergens in the sweat of 15 patients with atopic dermatitis, 10 patients with allergic rhinitis and high levels of specific IgE in the serum, and five patients with psoriasis without atopy as controls, by means of various commercial methods such as fluorescence immunoassay, nephelometry, chemiluminescence assay, enzyme immunoassay and the radioallergosorbent test. Total IgE and specific IgE antibodies were detectable in the sweat of patients with atopic dermatitis as well as of patients with allergic rhinitis alone. These levels of total IgE in the sweat correlated with the severity of the skin disease (P < 0.05). By means of the Ciba Corning assay (P < 0.001), the fluorescence immunoassay (P < 0.05) and the nephelometry assay (P < 0.05), positive correlations were then established between the levels of total IgE in the serum and the sweat. Moreover, specific IgE antibodies to birch pollen and Dermatophagoides pteronyssinus were detectable in the sweat and correlated positively with these specific IgE levels in the serum (P < 0.05). Further, the specific IgE levels against these allergens in the sweat also correlated with the severity of dermatitis (P < 0.05). It is suggested that these specific IgE antibodies against certain inhalant allergens in the sweat of patients with atopic dermatitis may play a role in allergen trapping in the skin.

Plasma retinol-binding protein levels of children under five years of age in a displaced Sudanese community.

Blood samples (100-160 microliters) were obtained from 1360 children by a finger prick in heparinized collection tubes, and an LC-Partigen retinol-binding protein (RBP) kit was used for quantification of RBP in the plasma. Only three boys and two girls had plasma RBP that was equal to or more than 3.0 mg/dL, a recommended cut-off point for normal values. The mean +/- SD) plasma RBP levels were at 1.150 +/- 0.613 mg/dL for boys (N = 689) and 1.233 +/- 0.572 mg/dL for girls (N = 671). The difference between boys and girls was statistically significant (p < 0.001). None of the children included in this study had eye signs of vitamin A deficiency. Two hundred eighty-two children (19.6%) received vitamin A supplements (200,000 IU) before the beginning of the study. The mean +/- SD for plasma RBP for children who received vitamin A supplement were 1.159 +/- .762 mg/dL for boys and 1.151 +/- 0.470 mg/dL for girls. The observed discrepancy between the biochemical and clinical manifestations of vitamin A deficiency was discussed.

Onset and evolution of stunting in infants and children. Examples from the Human Nutrition Collaborative Research Support Program. Kenya and Egypt studies.

The etiology of the early onset of stunting is diverse among populations of varying biological, environmental and cultural circumstances. This is exemplified within the Nutrition CRSP project, which took place in three different populations and ecological conditions. Within each study area a different mix and varying proportions of causative factors were identified. At least in Kenya, and probably in Mexico, the problem has its antecedents in prepregnancy and pregnancy. Powerful determinants of the infants' size at birth and during the first 6 months of life are maternal size upon entry into pregnancy, and weight and fat gain during pregnancy and lactation. In all three countries a low pregnancy weight gain was observed. Notably in Kenya, where the energy intake of the mother decreases progressively throughout pregnancy, not only do mothers gain only half as much as European or North American women, but they even lose weight and fat in the last month of pregnancy, and some mothers gain no weight or lose weight during the whole of pregnancy. Mothers in Kenya start lactation with relatively poor fat stores. Although their energy intake increases somewhat during lactation, preliminary estimates suggest that these increases may be insufficient to maintain their bodily integrity, to carry out their normal tasks of daily living, and to produce a sufficient amount of milk for optimal infant growth. In addition to an energy deficit, diet quality is a problem, particularly in Kenya and Mexico and less so in Egypt. Intakes of animal products and animal protein are very low. Zinc and iron intakes are not only low, but the bioavailability of these nutrients is poor because of the high phytate, fiber and tea content of the diet. Also vitamin B12 intake is extremely low, and at least mild-to-moderate iodine deficiency (IDD) is present in Kenya. The above micronutrients have been demonstrated to affect the linear growth of the Kenyan children, even after confounding factors have been controlled. The early use of supplemental feeding in Kenya is a double-edged sword. On the one hand, there is a slight increase in febrile illness and possible displacement of breast milk intake in the supplemented infants, although mothers do not decrease breast feeding frequency and duration. On the other hand, even the modest amounts of available zinc and B12 in supplemental foods appear to have a positive effect on linear growth.(ABSTRACT TRUNCATED AT 400 WORDS)

PIP: Findings from the Nutritional Collaborative Research Support Program (CRSP) in Kenya, Mexico, and Egypt demonstrate how the etiology of the early onset of stunting varies among populations of varying biological, environmental, and cultural circumstances. In Kenya, and probably Mexico, the problem has its antecedents in prepregnancy and pregnancy. Maternal size upon entry into pregnancy and weight and fat gain during pregnancy and lactation are powerful determinants of an infant's size at birth and during the first six months of life. Low pregnancy weight gain was observed in all three countries. Mothers in Kenya even lose weight and fat in the last month of pregnancy, with some gaining no weight or losing weight during the whole of pregnancy. Mothers in Kenya begin lactation with relatively poor fat stores, thus possibly unable to produce a sufficient amount of milk for optimal infant growth even though their energy intake increases somewhat during lactation. Intakes of animal products and animal protein are also low especially in Kenya and Mexico. Intakes of zinc, iron, vitamin B12, and iodine are low, and have been shown to affect the linear growth of the Kenyan children even after controlling for confounding factors. The early use of supplemental feeding in Kenya positively affects linear growth, yet increases febrile illness and possibly displaces breast milk intake in supplemented infants. Morbidity negatively affects attained length in six-month old infants and the rate of linear growth, while cultural patterns of child rearing also appear important for growth. A major deceleration of growth occurs in the first six months of life; from 18 months onward the quantity and quality of diet and environmental factors do not permit catch-up to the normal or near normal centiles observed in newborns.

Arg578Gln mutations in the von Willebrand factor gene in three unrelated cases of type IIB von Willebrand disease.

A recurrent heterozygous CGG-->CAG (Arg578Gln) mutation was detected in exon 28 of the von Willebrand factor gene in three additional unrelated families with inherited type IIB von Willebrand disease. This identical mutation showed a differential phenotypic expression in each family.

Interrelationship between diarrhea and vitamin A deficiency: is vitamin A deficiency a risk factor for diarrhea?

A cross-sectional study, a follow-up study and an evaluation of impact of community-based distribution of vitamin A capsules (200,000 IU) were conducted in Omdurman (Sudan) between November, 1988, and March, 1989. In the cross-sectional survey 1441 children less than 5 years of age participated, which established the baseline values for plasma retinol-binding protein. During the follow-up period 290 cases of diarrhea occurred. Low concentrations of plasma retinol-binding protein (less than 1.85 mg/dl) proved to be a risk factor for diarrhea, especially in girls. The relative risk increased after the second year of life. Children who received vitamin A supplementation before commencement of the study had a lower incidence of diarrhea. The protective effect of vitamin A supplementation was greater in girls (relative risk, 0.297; 95% confidence interval, 0.240 to 0.368) than in boys (relative risk, 0.404; 95% confidence interval, 0.352 to 0.464).

Characterization of grass pollen reactive T-cell lines derived from lesional atopic skin.

Since it has been hypothesized that atopic dermatitis represents a cellular immune reaction to exogenous aeroallergens, we investigated whether lesional skin contains allergen-specific T-cells and which lymphokines they might secrete. Using phytohaemagglutinin or grass pollen for the cloning procedure, we established a series of T-cell lines from the skin of two patients. When rechallenged with the allergen, three out of 12 dermal lines which had been cloned with the pollen extract and three out of 20 epidermal lines cloned with PHA were found to proliferate specifically. With one exception, allergen-specific lines were CD4+, CD8-, alpha/beta receptor +. The reaction pattern to the single components of the grass allergen extract was assessed with the line UH-D3. Further, the proliferative response to Lolium perennis was inhibited by HLA-DR antibody, indicating its dependence on structures of the MHC class II complex. Only one out of four CD4+ allergen-reactive lines secreted considerable interferon-gamma activity but all secreted interleukin-4. The relative predominance of IL-4 points to a possible role of skin-derived T-cells in the synthesis of IgE. The identification of allergen-specific T-cells in lesional skin of patients with atopic dermatitis is consistent with the hypothesis that their dermatitis represents a T-cell-mediated immune reaction.

Ascorbic acid deficiency and hepatic UDP-glucuronyl transferase. Qualitative and quantitative differences.

The effect of dietary ascorbate on hepatic UDP glucuronyltransferase (UDPGT) appears to be selective in that only certain isozymes of UDPGT are jeopardized. In this study, ascorbic acid deficiency produced a 68% reduction in the specific activity of hepatic UDPGT towards p-nitrophenol. Earlier studies showed a reduction in UDPGT activity towards p-aminophenol in ascorbate-deficient guinea pigs, whereas bilirubin and acetaminophen glucuronidation were unaffected. Kinetic studies suggest that p-aminophenol and p-nitrophenol are metabolized by a single isozyme in that p-nitrophenol was found to be a competitive inhibitor of p-aminophenol glucuronidation. Both qualitative and quantitative studies on partially purified UDPGT from ascorbate-deficient and ascorbate-supplemented guinea pigs were carried out to investigate the biochemical role of the vitamin. Qualitative differences were observed in UDPGT from ascorbate-deficient animals and included an increased lability to: thermal inactivation; storage at 4 degrees; and purification with UDP-glucuronic acid agarose column chromatography. Furthermore, an analysis of the microsomal membrane showed a 14% increase in membrane fluidity in ascorbate deficiency. Ascorbic acid added in vitro could not reverse the increase in fluidity observed in ascorbate-deficient microsomal membranes; however, ascorbylpalmitate, a more lipophilic form of the vitamin, was effective. Palmitic acid had no effect on membrane fluidity in microsomes from either the ascorbate-supplemented or ascorbate-deficient animals. This increase in membrane fluidity could not be explained by differences in cholesterol, total phospholipid, or phosphatidylcholine content of hepatic microsomes. Furthermore, a quantitative reduction in UDPGT partially purified from ascorbate-deficient guinea pigs was indicated by a marked reduction in protein banding at 55,000 daltons when compared to UDPGT partially purified from ascorbate-supplemented animals.

Bloqueio do plexo braquial pela via transaxilar com altas doses de lidocaína a 1,6% / Transarterial brachial plexux block using high doses of 1,6% lidocaine

El bloqueo del plexo braquial por la via transarterial fué realizado con dosis fijas de 50 ml de lidocaina a 1,6% con epinefrina a 1:200.000 en 20 pacientes sometidos a cirugía de las extremidades superiores. Fueron avaluados el tiempo de latencia, el porcentaje de éxito del bloqueo sensitivo y del bloqueo motor y la duración de la anelgesia. El índice de éxito fué de 95-100%, en ningún paciente fué necessário complementación con anestesia general, y no fueron observados señales de toxicidad sistémica de la lidocaina. La ausencia de analgesia fué verificada en apenas un paciente, en el trajecto cutáneo de los nervios ulnar y mediano. La durarión de la analgesia fué de 3,46 ñ 0,52 h

Histiocytosis X in an elderly patient. Ultrastructure and immunocytochemistry after PUVA photochemotherapy.

The clinical features of a 76-year-old man with histiocytosis X of the Letterer-Siwe type, with extensive skin involvement, are described. The patient's lesions responded dramatically to PUVA-photochemotherapy. Light microscopic, immunocytochemical and immunoelectron microscopic findings, before and after PUVA, are reported. Birbeck granules in phagolysosomes of dermal macrophages indicated uptake of destroyed HX cells. Residual HX cells in the skin and HX cells in a recurring lesion expressed the same membrane antigens as in the primary lesions.

Ascorbic acid deficiency and hepatic UDP-glucuronyltransferase.

The effect of dietary ascorbic acid on hepatic microsomal UDP-glucuronyltransferase (UDPGT) activity towards p-aminophenol, bilirubin, and acetaminophen was investigated. Ascorbate deficiency produced a 33% reduction in the specific activity of UDPGT towards p-aminophenol, whereas there was no difference between microsomes from ascorbate-deficient and supplemented guinea pigs in the activity towards bilirubin and acetaminophen. This suggests that the effect of the vitamin is on a specific isozyme. This reduction was correlated with the reduced quantity of hepatic microsomal cytochrome P-450, which has been previously reported for ascorbate-deficient guinea pigs. No difference was found in the apparent affinity for the substrate, p-aminophenol, or the cofactor, UDP-glucuronic acid. Differences in microsomal UDPGT activity towards p-aminophenol occurred between the two groups with membrane-perturbing processes such as sonication and Triton X-100. Sonication and magnesium chloride were found to increase activity 329% in ascorbate-supplemented animals and 138% in the ascorbate-deficient group. The addition of ascorbate acid in vitro, or its analog d-isoascorbic acid, could protect against the detrimental effects of excess substrate by maintaining a linear enzymatic rate over a 30-min time period; there was no significant effect on the initial rate of hepatic microsomal UDPGT activity in the ascorbate-supplemented animals whereas there was a significant increase in the ascorbate-deficient group. Glutathione was as effective as ascorbic acid in protecting against the detrimental effects of excess substrate whereas cysteine and dimethyltetrapteridine were only partially effective. Ascorbyl-2-sulfate and alpha-tocopherol had no significant effect.(ABSTRACT TRUNCATED AT 250 WORDS)

[Induction of subacute cutaneous lupus erythematosus by psoralen UV-A therapy]. / Induktion eines subakuten kutanen Lupus Erythematodes durch Psorale UV-A-Therapie.

We report on a 74-year-old female patient with psoriasis vulgaris who, under PUVA therapy, developed an exanthema with clinical and histological signs of systemic lupus erythematosus. Antibodies to Ro/SSA antigens were not detectable before the onset of the lupus exanthema but showed a high titer afterwards. At that time, we found the typical serological constellation of subacute cutaneous lupus erythematosus.

Gastric cancer detection in gastric ulcer disease.

A retrospective study has been performed of all cases of gastric ulcer diagnosed or investigated within the Endoscopy Unit of the Department of Medicine, Bristol, over a three year period (1974-76). The average length of follow-up was two years. Two hundred and sixty five cases of gastric ulcer were studied of which 37 proved to be malignant (14%). Presenting complaints of anorexia, weight loss, nausea and/or vomiting, and multiple (greater than 3) symptoms, were commoner in the malignant ulcer group. Ulcer site and the presence of coexisting duodenal ulceration were largely unhelpful in deciding the status of an ulcer. Malignant ulcers tended to be large (greater than 1 cm diameter). Radiology was highly unreliable in distinguishing benign from malignant ulcers. Visual inspection at endoscopy was more reliable, but associated with a tendency to over-diagnose malignancy. False positive biopsies were uncommon (two cases). Three cases of clinically unsuspected superficial gastric carcinoma were revealed. Repeated endoscopy and biopsy of all gastric ulcers until they are completely healed is advised.