Changing practice to improve pain control for renal patients.

Pain is a common symptom described by patients with end-stage kidney disease (ESKD) but remains ineffectively managed. The aim of this audit was to determine what proportion of these patients report pain, then introduce the use of an analgesic ladder adapted specifically for ESKD, and finally re-evaluate the prevalence of pain symptoms, looking for an improvement. A cohort of inpatients on the renal wards of a West London teaching hospital was studied. The number of patients reporting pain and the severity of their pain on a scale of 1-10 were recorded. A considerable number of patients were barred from participating because of a language barrier. Interpreters were introduced, and the phase was repeated. The World Health Organization (WHO) three-step analgesic ladder was adapted for patients with ESKD and introduced to medical staff on the renal wards. The number of patients reporting pain and the severity of their pain were re-recorded. There was a significant reduction in the number of patients reporting pain and the severity of their pain. Pain control in patients with ESKD is improved through the use of an adapted version of the WHO analgesic ladder. Strategies must be in place for effective communication with foreign patients.

A risk index for early node-negative breast cancer.

BACKGROUND: This study compared the application of the St Gallen 2001 classification with a risk index developed at the New South Wales Breast Cancer Institute (BCI Index) for women with node-negative breast cancer treated without adjuvant systemic therapy. METHODS: The BCI risk categories were constructed by identifying combinations of prognostic indicators that produced homogeneous low-, intermediate- and high-risk groups using the same variables as in the St Gallen classification. RESULTS: The BCI low-risk category consisted of women aged 35 years or more with a grade 1 oestrogen receptor (ER)-positive tumour 20 mm or less in diameter, or with a grade 2 ER-positive tumour of 15 mm or less. This category constituted 40.1 per cent of patients, with a 10-year distant relapse-free survival (DRFS) rate of 97.2 per cent. The BCI intermediate-risk category included women aged 35 years or more with a grade 2 ER-positive tumour of diameter 16-20 mm, or a grade 1 or 2 ER-negative tumour measuring 15 mm or less, and comprised 12.1 per cent of the women, with a 10-year DRFS rate of 88 per cent. The high-risk category comprised 47.7 per cent of women, with a 10-year DRFS rate of 68.4 per cent. CONCLUSION: If confirmed in other data sets, the BCI Index may be used to identify women at low risk of distant relapse (2.8 per cent at 10 years) who are unlikely to benefit from adjuvant systemic therapy, and women at intermediate risk of distant relapse (12 per cent at 10 years) in whom the benefit of adjuvant systemic therapy is small.

Histopathologic indicators of breast cancer biology: insights from population mammographic screening.

Histopathologic features of breast cancer such as tumour size, grade and axillary lymph node (LN) status variably reflect tumour biology and time. Recent evidence suggests that the biological character of breast cancer is established at an early stage and has a major impact on clinical course. The aim of this study was to distinguish the impact of biology on breast cancer histopathology by comparing features of breast cancers diagnosed following population mammographic screening with prevalent vs incident detection and screening interval. Central histopathology review data from 1147 cases of ductal in situ and/or invasive breast cancer were examined. Size, grade and LN status of invasive cancers were positively correlated (P < 0.001). Prevalent invasive cancers were larger (P < 0.001) and more likely to be LN positive (P = 0.02) than incident cases, but grade was not associated with screening episode (P = 0.7). Screening interval for incident cancers was positively associated with invasive cancer size (P = 0.05) and LN status (P = 0.002) but not grade (P = 0.1). Together, these data indicate that biology and time both impact on size and LN status of invasive breast cancer, but grade reflects biology alone. In view of the clinical importance of breast cancer biology, grade as its most direct indicator assumes particular significance.

Mechanical chest-wall vibration does not relieve air hunger.

Mechanical vibration of the chest wall can reduce dyspnea. It is unclear which sensations of respiratory discomfort are modulated by vibration (work/effort, air hunger, tightness). We performed two experiments to test whether vibration modifies air hunger: Experiment 1-eight adults performed six breath holds and rated their uncomfortable 'urge to breathe.' Vibration was applied separately at four chest-wall and two control sites, using two amplitudes. Breath-hold duration and ratings were unchanged by vibration at any site or amplitude. Experiment 2-nine adults were mechanically ventilated (mean 8.73 L/min) at constant hypercapnia (mean 48 mmHg) to produce mild to moderate ratings of air hunger (mean 37% of scale) with minimal respiratory muscle work. Vibration at 2nd or 3rd intercostal spaces during either inspiration or expiration did not change air hunger compared to triceps vibration. These experiments demonstrated that vibration does not relieve air hunger; we postulate that the effect of vibration is specific to the form of dyspnea.

Use of the St Gallen classification for patients with node-negative breast cancer may lead to overuse of adjuvant chemotherapy.

BACKGROUND: The 1998 St Gallen classification was devised to guide clinicians in the use of adjuvant systemic therapy for women with early breast cancer. In this study, the classification was applied to a historical group of patients with node-negative breast cancer who were treated without adjuvant therapy. METHODS: The St Gallen classification was applied to 421 women with breast cancer treated with conservative surgery and radiotherapy alone between 1979 and 1994. Primary tumour characteristics were reviewed centrally. RESULTS: When the most stringent version of the St Gallen classification was applied (grade 2 or 3 tumours classified as "high risk"), only 10 per cent of patients were "low risk", with a 10-year distant relapse-free survival (DRFS) rate of 100 per cent, and 15 per cent were at "intermediate risk" (10-year DRFS rate of 94 per cent). The high-risk group (75 per cent of women) had a 10-year DRFS rate of 77 per cent (P < 0.01). If the St Gallen classification had been applied to all patients in this series who were aged less than 70 years, up to 91 per cent would have been recommended to have chemotherapy. CONCLUSION: The St Gallen classification is an inaccurate measure of prognosis for patients with node-negative breast cancer and should be used with caution.

Treatment implications of a positive sentinel lymph node biopsy for patients with early-stage breast carcinoma.

BACKGROUND: Sentinel lymph node (SLN) mapping and biopsy is emerging as an alternative to axillary lymph node dissection (ALND) in determining the lymph node status of patients with early-stage breast carcinoma. The hypothesis of the technique is that the SLN is the first lymph node in the regional lymphatic basin that drains the primary tumor. Non-SLN (NSLN) metastasis in the axilla is unlikely if the axillary SLN shows no tumor involvement, and, thus, further axillary interference may be avoided. However, the optimal treatment of the axilla in which an SLN metastasis is found requires ongoing evaluation. The objectives of this study were to evaluate the predictors for NSLN metastasis in the presence of a tumor-involved axillary SLN and to examine the treatment implications for patients with early-stage breast carcinoma. METHODS: Between June 1998 and May 2000, 167 patients participated in the pilot study of SLN mapping and biopsy at Westmead Hospital. SLNs were identified successfully and biopsied in 140 axillae. All study patients also underwent ALND. The incidence of NSLN metastasis in the 51 patients with a SLN metastasis was correlated with clinical and pathologic characteristics. RESULTS: Of 51 patients with a positive SLN, 24 patients (47%) had NSLN metastases. The primary tumor size was the only significant predictor for NSLN involvement. NSLN metastasis occurred in 25% of patients (95% confidence interval [95%CI], 10-47%) with a primary tumor size 20 mm (P = 0.005). The size of the SLN metastasis was not associated significantly with NSLN involvement. Three of 7 patients (43%) with an SLN micrometastasis (< 1 mm) had NSLN involvement compared with 38 of 44 patients (48%) with an SLN macrometastasis (> or = 1 mm). CONCLUSIONS: The current study did not identify a subgroup of SLN positive patients in whom the incidence of NSLN involvement was low enough to warrant no further axillary interference. At present, a full axillary dissection should be performed in patients with a positive SLN.

Oscillation of the lung by chest-wall vibration.

Vibration of the thoracic surface has been shown to modify the drive to breathe and the sensation of dyspnea. It has been suggested that respiratory muscle afferents generate these effects. The possibility that the consequences of chest-wall vibration also involve intra-pulmonary afferents led us to investigate whether such vibration reaches the airways. Two vibratory stimuli were independently applied to four chest-wall sites and two control sites on eight healthy subjects. During separate breath holds, the vibrator was held on each site while subjects periodically opened and closed the pharynx. Airway pressure (P(AW)) was measured at the mouth. Spectral analysis of P(AW) showed pressure oscillations occurred at the same frequency as that of the vibrators when the pharynx was open; oscillation amplitude was vastly reduced when the pharynx was closed. Oscillation amplitude was also significantly larger during vibration at greater amplitude. These data demonstrate that vibration over the chest-wall vibrates the lung and could potentially excite intrapulmonary receptors.

Acute changes in carbon dioxide levels alter the electroencephalogram without affecting cognitive function.

The partial pressure of carbon dioxide in the arterial blood (PaCO2) is usually tightly regulated, yet it varies among healthy people at rest (range approximately 32-44 mmHg) as well as within an individual during many natural life situations. The present study examined whether modest changes in end-tidal PCO2 (PETCO2; a noninvasive measure of PaCO2) affect electroencephalographic (EEG) activity, cognitive function, and vigilance. Nine adults were ventilated mechanically using a mouthpiece; respiratory rate and breath size were held constant while PETCO2 was set to levels that produced minimal discomfort. Despite discrete changes in EEG, neither acute PETCO2 increases (mean = 47 mmHg) nor decreases (mean = 30 mmHg) from resting levels (mean = 38 mmHg) affected performance on cognitive tasks, latency or amplitude of the N1, P2, or P3 event-related potential, or alertness. Modest changes in PETCO2 may cause significant alterations in the EEG without disturbing cognitive function.

Recent developments in stereotactic breast biopsy methodologies: an update for the surgical pathologist.

Recently, there have been a number of new devices introduced for stereotactic biopsy of nonpalpable, mammographically detected lesions. The vacuum-assisted core biopsy (VACB) (Minimal Invasive Breast Biopsy (MIBB), U.S. Surgical, Norwalk, CT; Mammotome, Biopsys Medical, Cincinnati, OH) obtains multiple tissue cores (11-gauge) in a circumferential manner around the biopsy probe, inserted under stereotactic guidance. It provides more complete sampling of mammographic lesions than the conventional 14-gauge stereotactic core biopsy, reducing the number of unsatisfactory biopsies. The advanced breast biopsy instrumentation (ABBI) (United States Surgical Corporation, Norwalk, CT) system utilizes stereotactic technique and an oscillating blade-cutting mechanism to obtain a single large diameter (5 mm to 20 mm) tissue core, with the aim of obtaining an intact lesion in its entirety for histologic assessment. Its potential as a treatment option is still under investigation. Suggested protocols for specimen handling are presented together with a review of the recent literature. Close liaison with radiologists and surgeons performing these biopsies will allow the collection of further outcome data to evaluate the strengths and weaknesses of each technique.

Event-related potentials to inspiratory flow-resistive loads in young adults: stimulus magnitude effects.

Event-related potentials were recorded to brief presentations of four levels of inspiratory flow-resistive loads in young adults. We labeled the loads according to the level of resistance they provided subjectively: sub-threshold (0.34 cmH2O/l per s), near-threshold (4.01 cmH2O/l per s), intermediate (10.4cmH2O/l per s), and near-occlusion (57.5 cmH2O/l per s). No discernible ERPs were elicited by the undetected, sub-threshold stimulus but late components of the ERP (P2, N2, and P3) were observed to each of the three larger stimuli. They were related, in part, to behavioral judgments obtained during the stimulus periods. Both the latency and amplitude of the ERP components varied systematically as a function of stimulus magnitude, in a manner comparable to that observed in ERP paradigms using auditory and visual stimuli. Thus, the data show that event-related potentials to breathing are sensitive to physiologic effects of resistive loads present at the onset of inspiration. Respiratory ERPs may be used to infer sensory and perceptual responses to increases in airflow resistance and, accordingly, may relate to the perception of airflow obstruction in patient populations.

Self-control and external control of mechanical ventilation give equal air hunger relief.

Elevated end-tidal partial pressure of CO2 (PET(CO2)) causes air hunger; this sensation becomes intense with a relatively small rise in PET(CO2) if ventilation is held constant. Spontaneously breathing subjects increase ventilation in response to CO2, thereby greatly diminishing air hunger. In healthy subjects and ventilator-dependent patients, experimenter-induced increases in ventilator tidal volume (VT) relieve air hunger even if PET(CO2) is kept elevated. We addressed two questions: (1) Can paralyzed, ventilator-dependent patients use the sensation of air hunger to effectively control ventilator VT using nonrespiratory motor pathways; and (2) Do subjects obtain more relief when in control of their own ventilator? Four subjects were trained to increase ventilator VT using a mouth-operated switch. Subjects' ratings of air hunger intensity in response to elevated PET(CO2) were compared during three conditions: (1) constant VT; (2) subject-controlled VT; and (3) experimenter-controlled VT. When given control of their ventilator, all subjects increased VT in response to increased PET(CO2), thereby relieving air hunger. Air hunger relief was similar when the experimenter mimicked these VT changes. These results suggest that: (1) ventilator-dependent patients can use sensation, conscious decisions, and nonrespiratory motor pathways to achieve an appropriate respiratory response to increased PCO2 and (2) control of one's own ventilation is unimportant in these circumstances.

Generalized pustular psoriasis responsive to PUVA and oral cyclosporin therapy.

A patient with acute generalized pustular psoriasis was successfully treated with a combination of oral cyclosporin (6 mg/kg per day) and photochemotherapy (PUVA). Although early inpatient treatment with weak topical steroids and PUVA produced initial improvement, the patient's clinical condition fluctuated, with the subsequent development of erythroderma. The addition of oral cyclosporin produced dramatic improvement within 1 week of its commencement. The patient remained in remission 12 months following cessation of therapy.

Vesiculobullous Hailey-Hailey disease: successful treatment with oral retinoids.

A 56-year-old male presented with a pruritic, generalized vesiculobullous eruption. His past history revealed classical symptoms of limited Hailey-Hailey disease for 34 years. Clinically, vesicles, bullae and occasional pustules were present and multiple biopsies confirmed this to be an unusual presentation of Hailey-Hailey disease. Various therapeutic modalities including topical and oral antibiotics, oral prednisone and dapsone failed to achieve sustained remission. Treatment with low-dose oral etretinate (25 mg daily) produced marked clinical improvement with complete suppression of new vesicle formation after 6 weeks.

Air hunger induced by acute increase in PCO2 adapts to chronic elevation of PCO2 in ventilated humans.

Brief increases in arterial PCO2 (PaCO2) (lasting several minutes) produce a sensation of respiratory discomfort (air hunger). It is not known whether air hunger adapts to chronic changes in PaCO2. This study tested whether the level of end-tidal PCO2 (PETCO2) required to evoke air hunger would increase with chronic elevation of PETCO2 (lasting several days). Four ventilator-dependent subjects participated in a 2-wk study during which they were ventilated with air (placebo) or air rich in CO2 (CO2 exposure). Average resting PETCO2 during control periods was 25 Torr (typical for such patients); PETCO2 was 15 Torr higher during CO2 exposure. Ventilation and arterial PO2 did not differ between conditions. Periodically, we performed tests in which subjects rated the intensity of air hunger induced by brief increases in PETCO2. The increase in PETCO2 required to elicit a given air hunger rating during CO2 exposure also increased by approximately 15 Torr. That is, subjects' sensation of air hunger fully adapted to the chronic increase in PETCO2. Arterial pH did not fully return to control values during CO2 exposure. Accommodation in the chemoreceptors and neural pathways that subserve air hunger sensation may explain the adaptation of air hunger.

Black breast milk due to minocycline therapy.

We report the unusual case of a 29-year-old female who developed black discoloration of breast milk 3 weeks after commencing oral minocycline therapy for acne vulgaris. Histochemical analysis of the breast milk revealed the presence of pigment particles within macrophages with iron staining characteristics. We propose that the pigment may represent an iron chelate of minocycline or one of its derivatives.

Minocycline-induced hyperpigmentation in leprosy.

A 36-year-old man was treated with dapsone, rifampicin and clofazimine for borderline lepromatous leprosy. After 9 months, his leprosy plaques became progressively more red and after 23 months, the clofazimine was stopped and he was given minocycline instead. Six weeks later, he developed blue-black pigmentation in his leprosy lesions. The histology was consistent with minocycline-induced hyperpigmentation. This is the first report of minocycline-induced pigmentation in leprosy. We suggest it is important to consider this side-effect before the administration of minocycline in leprosy, particularly if it is prescribed in place of clofazimine.

Chrysiasis after low-dose gold and UV light exposure.

We describe a case of chrysiasis in a 54-year-old woman. The diagnosis was confirmed by light microscopy, transmission electron microscopy, and radiographic microanalysis. The condition developed after a relatively low dose of gold. We propose that chrysiasis developed because of the patient's exposure to the intense UV light in Australia.