Outcomes in achalasia from a surgical unit where pneumatic dilatation is first-line therapy.

The management of achalasia remains controversial, with little consensus on the optimal patient treatment pathway. In our own esophageal unit, we offer pneumatic dilatation as the initial therapy in most patients as first-line therapy. In this study, we aimed to examine the safety and efficacy of our own approach to the management of patients with a diagnosis of achalasia, examining symptomatic outcomes, patient satisfaction, and need for further intervention, as well as examining patient factors associated with treatment failure. Sixty-seven consecutive patients underwent pneumatic dilatation as first-line therapy (53% male, mean age 46 years). All attended regular outpatient follow-up (mean 37, range 3-132 months). Twenty-five percent of patients required a second intervention because of symptom recurrence, at a median period of 4.5 months. Symptomatic outcomes were excellent or good in 80%. Significant predictors of treatment failure and poor symptom score included a younger age at the time of diagnosis and increased esophageal diameter on barium swallow. This study suggests that pneumatic dilatation is a safe and effective approach as first-line therapy in patients with newly diagnosed achalasia.

Detection of human papillomavirus DNA in cytologically normal women and subsequent cervical squamous intraepithelial lesions.

BACKGROUND: Human papillomavirus (HPV) infection has been strongly associated with cervical carcinoma and its cytologic precursors, squamous intraepithelial lesions (SIL). We investigated the risk of SIL prospectively following polymerase chain reaction (PCR)-based DNA testing for a wide range of genital HPV types in a cohort of initially cytologically normal women, to clarify the role of HPV in the etiology of SIL. METHODS: Starting in April 1989, 17,654 women who were receiving routine cytologic screening at Kaiser Permanente (Portland, OR) were followed for the development of incident SIL. During follow-up, 380 incident case patients and 1037 matched control subjects were eligible for this nested case-control study. Cervical lavages collected at enrollment and, later, at the time of case diagnosis (or the corresponding time for selection of control subjects) were tested for HPV DNA using a PCR-based method. The data were analyzed as contingency tables with two-sided P values or, for multivariable analyses, using odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: In comparison with initially HPV-negative women, women who tested positive for HPV DNA at enrollment were 3.8 times (95% CI = 2.6-5.5) more likely to have low-grade SIL subsequently diagnosed for the first time during follow-up and 12.7 times more likely (95% CI = 6.2-25.9) to develop high-grade SIL. At the time of diagnosis, the cross-sectional association of HPV DNA and SIL was extremely strong (OR = 44.4 and 95% CI = 24.2-81.5 for low-grade SIL and OR = 67.1 and 95% CI = 19.3-233.7 for high-grade SIL). HPV16 was the virus type most predictive of SIL, even low-grade SIL. CONCLUSIONS: These findings are consistent with the hypothesis that HPV infection is the primary cause of cervical neoplasia. Furthermore, they support HPV vaccine research to prevent cervical cancer and efforts to develop HPV DNA diagnostic tests.

Thrombospondin-1 type 1 repeat recombinant proteins inhibit tumor growth through transforming growth factor-beta-dependent and -independent mechanisms.

Thrombospondin-1 (TSP-1) is a potent inhibitor of tumor growth and angiogenesis. The antiangiogenic activity of TSP-1 has been mapped to the procollagen homology region and the type 1 repeats (TSR) using synthetic peptides. To elucidate the molecular mechanisms that are involved in the inhibition of tumor growth by the TSRs, we have expressed recombinant versions of these motifs and have assayed their ability to inhibit the growth of experimental B16F10 melanomas and Lewis lung carcinomas. Recombinant proteins that contain all three TSRs (3TSR) or the second TSR with (TSR2+RFK) or without (TSR2) the transforming growth factor-beta (TGFbeta) activating sequence (RFK) have been expressed in Drosophila S2 cells. In addition, recombinant proteins with mutations in either the RFK sequence (TSR2+QFK) or the WSHWSPW sequence [TSR2 (W/T)] of the second TSR have been prepared. Similar to platelet TSP-1, these proteins are potent inhibitors of endothelial cell migration, and 3TSR of human TSP-1 (3TSR/hTSP-1) and TSR2+RFK activate TGFbeta. An 81% inhibition of B16F10 tumor growth is observed at 2.5 mg (135 nmol)/kg/day of the recombinant 3TSR/hTSP-1. A comparable level of inhibition is observed with 2.5 mg (360 nmol)/kg/day of TSR2+RFK. By contrast, 3TSR of mouse TSP-2 (3TSR/mTSP-2), TSR2+QFK, and TSR2 are significantly less effective. TSR2+RFK and TSR2 reduce tumor vessel density, but TSR2+RFK has a greater effect on B16F10 tumor cell apoptosis and proliferation. Concurrent treatment of B16F10 tumor-bearing mice with TSR2+RFK and either a soluble form of the TGFbeta receptor or an antibody to active TGFbeta reduces the inhibition of B16F10 tumor growth to levels that are comparable with those of TSR2 and TSR2+QFK. By contrast, the presence of the TGFbeta-activating sequence does not increase the level of inhibition of Lewis lung carcinoma experimental tumor growth. These data indicate that the TSRs inhibit tumor growth by inhibition of angiogenesis and regulation of tumor cell growth and apoptosis. The regulation of tumor cell growth and apoptosis is TGFbeta dependent, whereas the inhibition of angiogenesis is not.

Interleukin 2 production in vitro by peripheral lymphocytes in response to human papillomavirus-derived peptides: correlation with cervical pathology.

Human papillomavirus (HPV) is believed to be the major cause of cervical cancer. To investigate whether a cellular immune response, especially a T helper type 1 response, is related to the natural defense against HPV-related cervical lesions, the interleukin 2 response of peripheral blood lymphocytes in vitro to overlapping peptides from HPV-16 E6 and E7 oncoproteins was compared with the degree of cervical cytological abnormality among 140 women in a cross-sectional study. We compared 66 women diagnosed with low-grade squamous intraepithelial lesions (LSIL), 21 with high-grade squamous intraepithelial lesions (HSIL), and 28 with invasive cervical cancer with 25 women who were cytologically normal but previously HPV-16 DNA positive. The fraction showing strong interleukin 2 production against HPV-16 peptides was greatest among cytologically normal women (35%) and declined with increasing disease severity [LSIL] (20%), HSIL, (17%), and cancer patients (7%); X2 test P for the trend = 0.02], whereas the responses against a recall influenza antigen were not significantly different among groups. Our finding suggests that a T helper lymphocyte type 1 response to HPV antigens is associated with disease status. This result may reflect a targeted effect of the disease on immune function or a protective effect of the immune response against disease progression.

MHPG excretion in endogenous depression: relationship to clinical state and the effects of ECT.

In a group of 70 patients with endogenous depression entering a controlled trial of real versus sham ECT, urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion was significantly reduced by comparison with previously studied groups of control subjects, of acute and chronic schizophrenic patients and of anxious patients. However, urinary MHPG was unrelated to severity of depression, or to the presence of delusions, retardation or agitation. MHPG excretion did not predict clinical outcome, or the response to ECT. Urinary MHPG content at trial entry was unrelated to past tricyclic antidepressant or benzodiazepine medication, although an influence of the latter on the findings cannot be excluded, since all patients received benzodiazepine (nitrazepam) night sedation during the trial. During the 4-week trial MHPG excretion remained low and did not increase in relation to change in clinical state, although there was a small but significant increase in patients who received real ECT. The findings confirm that urinary MHPG excretion is reduced in depression, but establish that such reductions are not state dependent. Since the increase in MHPG excretion with ECT is not related to changes in clinical state, the former presumably does not reflect the mechanism of action of ECT.

Prophylactic aluminium hydroxide and hyperaluminaemia in intensive care.

Prophylactic antacid therapy is widely used in intensive care units. We show that significant hyperaluminaemia may occur during the course of prophylaxis with aluminium hydroxide in patients with compromised renal function. Since a significant proportion of patients in intensive care have, or are at risk of developing, renal failure we suggest that the routine use of aluminium hydroxide should be avoided.

Cutaneous malignant melanoma: nursing's role in prevention and early detection.

The incidence of cutaneous malignant melanoma (CMM) is increasing at an alarming rate. Risk factors that may contribute to the increase include ultraviolet (UV) radiation, lack of skin pigmentation, and genetic, hormonal, and immunologic factors. Although the exact nature of the relationship between melanoma and UV radiation is unclear, evidence suggests a correlation between sun exposure and CMM incidence. Caucasians with fair skin who sunburn and freckle easily and individuals with numerous nevi or moles and/or atypical nevi or moles are also at increased risk of CMM. Melanoma almost always is curable by surgery if it is detected early. Nursing can make a major contribution to reducing the morbidity and mortality of CMM both through educating the public in prevention and early detection measures and by screening individuals for suspicious lesions.

A comparison of some retrograde and anterograde effects of electroconvulsive shock in patients with severe depression.

Seventy severely depressed patients were randomly assigned to receive either a standard course of bilateral electroconvulsive therapy (ECT) or a course of simulated ECT (muscle relaxant and anaesthesia) identical to the real course except that the shock was omitted. Anterograde amnesia due to the shock was demonstrated in recognition memory for word lists and in recall of labels for faces, but this was eliminated by priming. Retrograde amnesia was also present for labels for faces learned the day before a treatment, but this was not eliminated by priming. Recognition memory for material learned in the remote past was better in the patients who had received shock than in those who had received only anaesthetic.

Junior medical staff and the assessment of trauma.

Eighty junior doctors in the acute specialties received a postal questionnaire aimed at assessing their ability to assign priority to the treatment of patients who may have sustained serious trauma. Forty-eight doctors (60%) replied. Of these, three doctors (6%) correctly assigned all patients; 44% failed to identify the three patients in most urgent need of treatment.

As seen on TV: observational study of cardiopulmonary resuscitation in British television medical dramas.

OBJECTIVE: To determine the frequency and accuracy with which cardiopulmonary resuscitation is portrayed in British television medical dramas. DESIGN: Observational study. SUBJECTS: 64 episodes of three major British television medical dramas: Casualty, Cardiac Arrest, and Medics. MAIN OUTCOME MEASURES: Frequency of cardiopulmonary resuscitation shown on television; age, sex, and diagnosis of the patients undergoing resuscitation; rate of survival through resuscitation. RESULTS: Overall 52 patients had a cardiorespiratory arrest on screen and 3 had a respiratory arrest alone, all the arrests occurring in 40 of the 64 episodes. Of the 52 patients having cardiorespiratory arrest, 32 (62%) underwent an attempt at cardiopulmonary resuscitation; 8 attempts were successful. All 3 of the patients having respiratory arrests alone received ventilatory support and survived. On 48% of occasions, victims of cardiac arrest seemed to be less than 35 years old. CONCLUSIONS: Cardiorespiratory resuscitation is often depicted in British television medical dramas. Patients portrayed receiving resuscitation are likely to be in a younger age group than in real life. Though the reasons for resuscitation are more varied and more often associated with trauma than in reality, the overall success rate is nevertheless realistic. Widespread overoptimism of patients for survival after resuscitation cannot necessarily be blamed on British television medical dramas.

Pulmonary occlusion (wedge) angiography in adult respiratory distress syndrome. A survey of angiographic appearances and outcomes.

Pulmonary occlusion angiography was performed in 34 patients admitted to the intensive therapy unit with a diagnosis of adult respiratory distress syndrome. Twenty angiograms were normal. Ten patients survived. No patient with abnormal angiography survived.