The variation in breast density and its relationship to delayed wound healing: a prospective study of 40 reduction mammoplasties.

The proportions of glandular and adipose tissue within the breast vary. This study records the variation in density of breast tissue excised at 40 consecutive bilateral breast reductions. Age, body mass index (BMI), breast size and wound healing problems were related to breast density. The removed breast tissue was weighed and volume determined by water displacement. Delayed wound healing was defined as any breast unhealed after 2 weeks. The density of excised tissue varied between 0.8 and 1.2g/cm(3). There was no correlation between age or BMI and breast density. Delayed wound healing occurred in 32% of patients. There was no correlation between delayed wound healing and breast density. However, there was a direct relationship between increasing BMI and delayed wound healing. In this study, breast density varied by up to 50%. The density of breast tissue cannot be predicted by age, BMI or breast size. There is no relationship between delayed wound healing and breast density.

An approach to complex tracheostomal complications.

Fistula formation following laryngectomy, most commonly pharyngocutaneous, is the most feared non-fatal complication with an incidence range from 5 to 30%. Tracheoesophageal fistulae are rare and are, most often, associated with the creation of a surgical speech fistula or the stomal recurrence of a malignant tumour. We present five cases of complex post-laryngectomy fistulae and a new approach to management. We advocate debridement of infected or necrotic tissue, primary suture of the oesophageal and tracheal defects with interposition of healthy viable tissue as a free transfer. If necessary, the trachea can be mobilised and the tracheostome is lowered to healthy tissue outside the radiotherapy field, with excision of the manubrium and hemi-clavicles. This technique allows reconstruction as a single stage procedure and does not preclude the future creation of a further tracheoesophageal fistula for voice rehabilitation.

Klippel Trenauney syndrome and reduction mammoplasty.

Klippel Trenauney syndrome is a rare congenital abnormality that includes extremity hypertrophy. We report an unusual case of breast asymmetry due to unilateral chest and limb hypertrophy and describe successful unilateral breast reduction. We highlight the potential problems of surgery within this group and a management approach to minimise complications.

CD8+ T cells control Th2-driven pathology during pulmonary respiratory syncytial virus infection.

BALB/c mice vaccinated with vaccinia virus expressing the major surface glycoprotein G of respiratory syncytial virus (RSV) develop lung eosinophilia during RSV challenge. The G protein is remarkable in that it induces CD4+, but no CD8+ T cells in this mouse strain. Studies using passive T cell transfers show that co-injection of CD8+ T cells greatly reduces the Th2-driven lung eosinophilia caused by G-specific CD4+ T cells. By contrast, vaccination with the fusion protein (F) induces both CD8+ and CD4+ T cells, but not lung eosinophilia during RSV infection. These observations suggest that CD8+ T cells play a crucial role in preventing Th2-driven pathology. We therefore depleted mice with anti-CD8 antibodies in vivo. This treatment allowed lung eosinophilia to develop in F-primed mice. Depletion of interferon (IFN)-gamma had a similar effect, suggesting that secretion of this cytokine is the mechanism by which CD8+ T cells exert their effect. To test whether similar effects occurred in other strains of mice, RSV-infected C57BL/6 mice (which do not develop eosinophilia after sensitization to G) were treated with anti-IFN-gamma. Again, these mice developed eosinophilia. In this strain, genetic deletion of CD8-alpha, beta2-microglobulin or genes coding for the transporter associated with antigen presentation (which in each case eliminates CD8+ T cells) caused lung eosinophilia during RSV infection. These studies show the critical roles that CD8+ T cells and IFN-gamma production play in regulating Th2-driven eosinophilia and provide a unifying explanation for previous studies of lung eosinophilia. We propose that vaccines designed to enhance CD8+ T cell recognition might avoid disease caused by CD4+ Th2 cells.

Adrenocortical function in the domestic cat during treatment with levonorgestrel.

Levonorgestrel was administered via a subcutaneous, slow-release silastic implant to 10 queens. Five other queens served as controls. Their adrenocortical function was assessed by the adrenocorticotrophic hormone (ACTH) stimulation test before and after one, two, six and 12 months of treatment. In addition, the gross anatomy and histology of the adrenal gland were examined post mortem in six of the treated cats. In both the control and treated queens the plasma cortisol concentrations (pre and post ACTH) were significantly different (P < 0.05) at different times. However, there were no significant differences between the plasma cortisol concentrations (pre and post ACTH) of the treated and control queens. No gross or microscopical abnormalities were visible in the adrenal glands of the treated queens.

Probable recurrent femoral artery thrombosis in a dog with intestinal lymphosarcoma.

An 11-year-old mixed-breed dog was examined because of chronic diarrhea, anorexia, and weight loss. Clinicopathologic abnormalities included anemia and hypoalbuminemia, and protein-losing enteropathy was identified. Acute, unilateral, femoral artery thrombosis developed before the cause of the protein-losing enteropathy could be identified. The dog was treated with aspirin, and sensation and function of the affected limb returned over the next 5 days, but thrombosis of the opposite femoral artery then developed. The dog was euthanatized, and at necropsy, intestinal lymphosarcoma was the only disease process found. Although disseminated intravascular coagulation is a well-recognized potential complication of neoplasia in dogs, recurrent localized thrombosis, as in this dog, also can develop.

The contraceptive effects of levonorgestrel in the domestic cat.

The effects of subdermal implantation of levonorgestrel (LNG) on reproduction were studied in domestic cats (Felis domestica). Levonorgestrel was administered via a slow-release subdermal silastic implant to 10 queens. The implants contained 16 mg of LNG and were designed to release 60 micrograms of the drug daily. Each treated queen received one implant. Five queens (control, group 1) received subdermal silastic implants containing no drug. Changes in body weight, mammary gland structure (determined by palpation), serum blood glucose concentrations, and reproductive factors (occurrence of estrous cycles, serum progesterone concentrations, and pregnancy) were monitored for 1 year. Four treated queens (treatment/recovery, group 2) were used to investigate reproductive function following 12 months of LNG treatment. To assess effects of treatment on macroscopic and microscopic anatomic features of reproductive and nonreproductive tissues, the remaining six cats (treatment/histology, group 3) were studied. Hemiovariohysterectomy was performed in two queens each at 0, 2, and 6 months of the study. Later, the remainder of the reproductive tract was harvested at necropsy (two after 2 months of treatment, two after 6 months, two after 12 months) to assess change in individual queens. Nonreproductive tissues were also examined at necropsy to determine effects of LNG in these six queens. All queens retained the implants during the period of study without detectable discomfort. Estrus was suppressed and no pregnancies were recorded in the four LNG-treated cats that were housed with a male. Treatment with LNG had no effect on body weight, physical mammary gland structure, or serum blood glucose concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute tularemia in three domestic cats.

Acute Francisella tularensis infection in 3 domestic cats was presumptively diagnosed on the basis of clinical signs and lesions and confirmed by culturing or immunofluorescent demonstration of the organism. Clinical findings include marked signs of depression, oral/lingual ulceration, regional or generalized lymphadenomegaly, hepatosplenomegaly, panleukopenia with severe toxic change of neutrophils, and hyperbilirubinemia with bilirubinuria. Lesions found at necropsy included icterus, oropharyngeal and lingual ulceration, multiple foci of necrosis in lymph nodes, spleen, liver, and lung, and severe segmental or diffuse enterocolitis. Results of serologic testing for F tularensis was positive in only 1 of the 3 cats. The organism was cultured aerobically from several tissues, including aspirated bone marrow obtained before death in 1 cat. Results of an indirect fluorescent antibody test, performed on fresh and formalin-fixed tissues of all cats, were positive. Because of the severe clinical course, opportunity to evaluate therapeutic regimens was not possible. Until now, confirmed diagnosis of feline tularemia only has been made retrospectively, in instances when cats were suspected to have transmitted infection to human beings in whom the primary diagnosis was made. The findings in this report provide a basis for presumptive diagnosis that will help to minimize public health risk associated with this potentially fatal zoonotic disease.

Electrocardiographic abnormalities associated with tetanus in two dogs.

Bradycardia, sinus arrest, and second-degree atrioventricular block developed in 2 dogs with tetanus. Clinical signs attributable to bradycardia were not apparent. Administration of atropine resulted in resolution of the arrhythmias. Both dogs responded well to supportive treatment; the bradycardia resolved within 4 days of onset without specific treatment. Tetanus should be included in the differential diagnosis when increased neuromuscular excitability and bradycardia are evident, as is found in toxicity with acetylcholinesterase inhibitors, increased intracranial pressure, and other neurologic disorders.

Autosomal recessive inherited phosphofructokinase deficiency in English springer spaniel dogs.

Three families of English springer spaniel dogs with phosphofructokinase (PFK) deficiency causing haemolysis were studied. Four male dogs and one female dog with chronic haemolysis and haemolytic crises were found to have markedly reduced PFK activity in erythrocytes (8-20% of control English springer spaniels). PFK-deficient erythrocytes exhibited an extreme alkaline and sucrose lysis. The oxygen dissociation curve of erythrocyte suspensions was shifted to the left with a 50% saturation of haemoglobin at a partial oxygen pressure of 16-17 mmHg (normal 26-31 mmHg). Muscle wasting and mildly increased serum creatine phosphokinase activity were also noted. Six clinically normal first degree relatives of affected dogs had erythrocyte PFK activities that were 38-51% of controls. In these family members, there was an erythrocytosis and mild reticulocytosis probably due to a mildly enhanced haemoglobin-oxygen affinity but no increase in serum creatine phosphokinase. These studies confirm the familial nature of muscle-type PFK deficiency in English springer spaniels and support the conclusion that this animal model of the human glycogen storage disease type VII is inherited as an autosomal recessive trait.

Action of intravenously administered aminophylline on normal airways.

The changes in airway caliber and plasma cyclic-AMP levels after intravenously administered aminophylline, and the effect of DL- and D-propranolol on these responses have been investigated in a double-blind manner in normal subjects. Aminophylline 5.6 mg/kg was given intravenously over a 10-min period and the airway response was measured as change in specific airway conductance (delta SGaw) in the body plethysmograph. In the initial study in 6 subjects, orally administered placebo or propranolol was followed 2 h later by intravenously administered aminophylline. Neither placebo nor propranolol alone caused any change in SGaw at 2 h. After placebo, intravenously injected aminophylline produced a 30% increase in SGaw, reaching a peak 5 min after injection. This response was equivalent to 77% of the maximal response to 400 micrograms inhaled albuterol in the same subjects. After propranolol, the airway response to aminophylline was attenuated, with a 53% reduction in delta SGaw at the time of peak response. In a further study on 6 subjects, intravenously given aminophylline produced a 25% increase in SGaw and a 51% increase in plasma cyclic-AMP levels after placebo tablets. Pretreatment with 40 and 80 mg DL-propranolol caused a dose-dependent reduction of both the airway and plasma cyclic-AMP response to aminophylline. The airway response to aminophylline was not attenuated by D-propranolol so the effect of DL-propranolol is thought to be due to beta-adrenoceptor blockade. The absence of any detectable change in SGaw after DL-propranolol suggests there is little resting sympathetic tone to the airways in normal subjects. In the absence of sympathetic stimulation, the rapid response to aminophylline is unlikely to be due to phosphodiesterase inhibition. The attenuation of the airway and cyclic-AMP response by propranolol suggests that part of the action of aminophylline may be due to beta-agonist activity.

Bronchial and cardiac beta-adrenoceptor blockade--a comparison of atenolol, acebutolol and labetalol.

Bronchial and cardiac beta-adrenoceptor blockade have been compared in six normal subjects after three beta-adrenoceptor antagonists. Single and double doses of atenolol (50 and 100 mg), acebutolol (100 and 200 mg) and labetalolol (150 and 300 mg) were studied on separate occasions. 2 Salbutamol airway dose-response curves were obtained by measuring the airway response as the change in specific airway conductance (sGaw) after increasing doses of inhaled salbutamol. Bronchial beta-adrenoceptor blockade was assessed after each drug as the dose of salbutamol needed to cause a 50% increase in sGaw (sGaw D50). 3 Cardiac beta-adrenoceptor blockade was assessed after the same doses of each beta-adrenoceptor antagonist, by measuring the percentage reduction in exercise heart rate from control, after exercise for 5 min at 70% of the subject's maximum work rate. 4 Atenolol 50 and 100 mg caused least bronchial beta-adrenoceptor blockade and the greatest reduction in exercise heart rate. 5 Acebutolol 100 and 200 mg and labetalol 150 and 300 mg produced more bronchial beta-adrenoceptor blockade than atenolol. 6 With this approach new beta-adrenoceptor antagonists can be assessed without putting asthmatic patients at risk.

Airway and metabolic responsiveness to intravenous salbutamol in asthma: effect of regular inhaled salbutamol.

1. Airway, metabolic and cyclic nucleotide responses to intravenous salbutamol were measured in five patients with mild asthma who had taken no medication in the week before the study. The studies were repeated after the patient had taken regular inhaled salbutamol for 4 weeks, in doses increasing to 2000 micrograms daily in week 4. 2. The pretreatment airway, metabolic and cyclic nucleotide responses to salbutamol were similar to those previously reported in normal subjects. These patients therefore did not show evidence of partial beta-adrenoceptor blockade. 3. After 4 weeks' salbutamol therapy the airway response to intravenous salbutamol was unchanged. 4. The glucose, pyruvate and adenosine 3':5'-cyclic monophosphate (cyclic AMP) responses to intravenous salbutamol were depressed after regular salbutamol administration. The dose-response curve for non-esterified fatty acids and insulin, though displaced downwards, did not indicate an impaired response to salbutamol since the shape was unchanged. There was no significant change in the lactate, glycerol and total ketone response. 5. This study confirms that tissues differ in the ease with which they develop resistance to beta-adrenoceptor agonists. Asthmatic airways appear to be relatively protected from developing assistance when compared with other tissues in asthmatic patients and when compared with the airways of normal subjects.

Assessment of bronchial beta blockade after oral bevantolol.

We have applied a new method for quantitative measurement of bronchial beta adrenoceptor blockade to a new beta adrenoceptor antagonist, bevantolol. Dose-response curves to a beta agonist, albuterol, were obtained in six normal subjects by measuring specific airway conductance (sGaw) after increasing doses of inhaled albuterol. These were repeated on three separate occasions 2 hr after subjects had taken oral placebo or bevantolol (75 or 150 mg), double-blind in random order. The dose-response curves after bevantolol 75 mg were displaced in the right of placebo in four subjects and after 150 mg were displaced to the right of placebo in all subjects. The mean dose ratios for bevantolol 75 or 150 mg were 1.02 and 2.77, much the same as those obtained in the same subjects after practolol 100 and 200 mg and considerably less than that after propranolol 40 mg. The mean reductions in exercise heart rate were 25% and 29% after bevantolol 75 and 150 mg. Our data show that bronchial beta blockade after a beta blocking drug can be assessed quantitatively in many by a double-blind technique.

Quantitative assessment of bronchial beta-adrenoceptor blockade in man.

1. We describe a method for assessing bronchial beta-adrenoceptor blockade quantitatively in man. Specific airway conductance is measured after increasing doses of inhaled salbutamol and the extent to which the dose-response curve is displaced to the right after beta-adrenoceptor blocking drugs is used to assess bronchial beta-adrenoceptor blockade. 2. Salbutamol dose-response curves were plotted for six normal subjects by measuring sGaw 15 min after increasing doses of inhaled salbutamol. Salbutamol produced a 30-70% increase in sGaw. 3. Salbutamol dose response curves were obtained 2 h after oral practolol (100 mg and 200 mg) and oral propranolol (40 mg and 80 mg) on separate days and were displaced to the right. 4. The mean dose ratios for practolol 100 mg and 200 mg were 1.2 and 2.1 and for propranolol 40 mg and 80 mg they were 21 and 61 respectively.

beta-adrenergic agonist resistance in normal human airways.

The response to a beta2-agonist (salbutamol) was assessed by measuring specific airways conductance (sGaw) in healthy volunteers following increasing doses of inhaled or intravenous salbutamol. Regular inhaled salbutamol in doses exceeding 200 microgram four times a day produced a progressive loss of airways responsiveness to both inhaled and intravenous salbutamol (beta-agonist resistance). In salbutamol-resistant subjects full bronchodilator sensitivity was restored 3-5 h after intravenous hydrocortisone.