Reoperation for disruption and recurrence after Nissen fundoplication.

This report deals with 25 failed Nissen operations. A method of classifying the type of failure is presented. Manometric studies document disordered motor activity in ten of these patients with return to normal activity after repair. With these difficult patients, intraoperative manometrics allowed a satisfactory antireflux barrier to be created with posterior gastropexy. Good to excellent results were achieved in 22 of 24 patients. A search of the world literature is presented with complications ranging from the well-known "gas-bloat" syndrome to potentially lethal fistulas.     

Variations in T1 and T2 relaxation times of normal appearing white matter and lesions in multiple sclerosis

OBJECTIVE: To investigate the variation in T1 and T2 relaxation times of normal appearing white matter (NAWM) and lesions in multiple sclerosis (MS) throughout the brain. BACKGROUND: The magnetic resonance imaging (MRI) sequence fast FLAIR (fluid attenuated inversion recovery) has demonstrated overall increased lesion detection when compared to conventional or fast spin echo (FSE) but fewer lesions in the posterior fossa and spinal cord. The reasons for this are unknown, but may be due to variations in the T1 and T2 relaxation times within NAWM and MS lesions. METHOD: Ten patients and 10 controls underwent MRI of the brain which involved FSE, fast FLAIR and the measurement of T1 and T2 relaxation times. RESULTS: Of 151 lesions analysed (22 infra-tentorial, 129 supra-tentorial), eight were missed by the fast FLAIR sequence. T1 and T2 relaxation times in normal controls were longer in the infra-tentorial, than supra-tentorial, region. Patient NAWM relaxation times were prolonged compared with control values in both regions. Lesions demonstrated longer relaxation times than either control white matter or patient NAWM in both regions, however this difference was less marked infra-tentorially. The eight posterior fossa lesions not visible on the fast FLAIR sequence were characterised by short T1 and T2 relaxation times which overlapped with the patient NAWM for both T1 and T2 and with control values for T2 relaxation times. CONCLUSION: Both lesion and NAWM relaxation time characteristics vary throughout the brain. The T1 and T2 relaxation times of infra-tentorial lesions are closer to the relaxation times of local NAWM than supra-tentorial lesions, resulting in reduced contrast between posterior fossa lesions and the background NAWM. Consequently the characteristics of some lesions overlap with those of NAWM resulting in reduced conspicuity. By utilising this information, it may be possible to optimise fast FLAIR sequences to improve infra-tentorial lesion detection.     

Planum temporale, planum parietale and dichotic listening in dyslexia

A reduction or reversal of the normal leftward asymmetry of the planum temporale (PT) has been claimed to be typical of dyslexia, although some recent studies have challenged this view. In a population-based study of 20 right-handed dyslexic boys and 20 matched controls, we have measured the PT and the adjacent planum parietale (PP) region in sagittal magnetic resonance images. For the PT, mean left and right areas and asymmetry coefficients were compared. Since a PP area often could not be identified in one or both hemispheres, a qualitative comparison was used for this region. The total planar area (sum of PT and PP) was also compared between the two groups. A dichotic listening (DL) test with consonant–vowel syllables was administered to assess functional asymmetry of language. The results showed a mean leftward PT asymmetry in both the dyslexic and the control group, with no significant difference for the degree of PT asymmetry. Planned comparisons revealed however, a trend towards smaller left PT in the dyslexic group. In control children, but not in the dyslexic children, a significant correlation between PT asymmetry and reading was observed. A mean leftward asymmetry was also found for the total planar area, with no difference between the groups for the degree of asymmetry. Significantly fewer dyslexic children than control children showed a rightward asymmetry for the PP region. Both groups showed a normal right ear advantage on the DL task, with no significant difference for DL asymmetry. No significant correlation was observed between PT asymmetry and DL asymmetry. The present population-based study adds to recent reports of normal PT asymmetry in dyslexia, but indicates that subtle morphological abnormalities in the left planar area may be present in this condition.     

Premature treatment termination by angry patients with combat-related post-traumatic stress disorder

Angry patients with conjoined post-traumatic stress disorder often direct their anger at health care providers during the course of treatment. Such misplaced anger can interfere with treatment. Emerging treatments for trauma-related anger are effective. However, even in the course of psychotherapy for trauma-related anger, these patients direct anger at their therapists, compromising the treatment alliance and increasing the likelihood of premature termination. A case example is presented to illustrate the effect of anger on the treatment alliance. A therapeutic strategy is proposed to reduce the likelihood of premature treatment termination in these high-risk patients. This strategy may also be helpful in primary care contexts.     

Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. I: maternal and prenatal evaluations.

The maternal and developmental toxicities of perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. PFOS is an environmentally persistent compound used as a surfactant and occurs as a degradation product of both perfluorooctane sulfonyl fluoride and substituted perfluorooctane sulfonamido components found in many commercial and consumer applications. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestational day (GD) 2 to GD 20; CD-1 mice were similarly treated with 1, 5, 10, 15, and 20 mg/kg PFOS from GD 1 to GD 17. Controls received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg for mice). Maternal weight gain, food and water consumption, and serum chemistry were monitored. Rats were euthanized on GD 21 and mice on GD 18. PFOS levels in maternal serum and in maternal and fetal livers were determined. Maternal weight gains in both species were suppressed by PFOS in a dose-dependent manner, likely attributed to reduced food and water intake. Serum PFOS levels increased with dosage, and liver levels were approximately fourfold higher than serum. Serum thyroxine (T4) and triiodothyronine (T3) in the PFOS-treated rat dams were significantly reduced as early as one week after chemical exposure, although no feedback response of thyroid-stimulating hormone (TSH) was observed. A similar pattern of reduction in T4 was also seen in the pregnant mice. Maternal serum triglycerides were significantly reduced, particularly in the high-dose groups, although cholesterol levels were not affected. In the mouse dams, PFOS produced a marked enlargement of the liver at 10 mg/kg and higher dosages. In the rat fetuses, PFOS was detected in the liver but at levels nearly half of those in the maternal counterparts, regardless of administered doses. In both rodent species, PFOS did not alter the numbers of implantations or live fetuses at term, although small deficits in fetal weight were noted in the rat. A host of birth defects, including cleft palate, anasarca, ventricular septal defect, and enlargement of the right atrium, were seen in both rats and mice, primarily in the 10 and 20 mg/kg dosage groups, respectively. Our results demonstrate both maternal and developmental toxicity of PFOS in the rat and mouse.     

Early discharge for patients with exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial

BACKGROUND: We have previously reported the use of a hospital based respiratory nurse service (Acute Respiratory Assessment Service, ARAS) to support home treatment of patients with exacerbations of chronic obstructive pulmonary disease (COPD). A controlled trial was undertaken to compare early discharge with home treatment supported by respiratory nurses with conventional hospital management of patients admitted with exacerbations of COPD. METHODS: Patients with COPD admitted as emergencies were identified the next working day. They were eligible for inclusion in the study if the differential diagnosis included an exacerbation of COPD, but were excluded if other medical conditions or acidotic respiratory failure required inpatient investigation or management. Of 360 patients reviewed, 209 were being assessed for other active medical problems and were excluded, 33 potential participants were already involved in research studies and so were ineligible, and 37 did not wish to participate in the study. Eighty one patients were randomised to receive conventional inpatient care (n=40) or to planned early discharge the next working day (n=41). Those discharged early continued treatment at home under the supervision of specialist respiratory nurses. Outcome measures were readmission, additional hospital days, and deaths within 60 days of initial admission. Process measures included number of visits, duration of follow up by the respiratory nurse, and additional treatment provided to support early discharge. RESULTS: On an intention to treat basis, a policy of early discharge reduced inpatient stay from a mean of 6.1 (range 1-13) days with conventional management to 3.2 (1-16) days with an early discharge policy. Twelve patients (30% conventional management, 29.3% early discharge) were readmitted in each group giving a mean difference in readmission of 0.7% (95% CI of the difference -19.2 to 20.6). In the conventional management group readmitted patients spent a mean of 8.75 additional days in hospital compared with 7.83 days in the early discharge group, giving a mean difference of 0.92 days (95% CI of the difference -6.5 to 8.3). There were two deaths (5%) in the conventional management group and one (2.4%) in the early discharge group, a mean difference of 2.6% (95% CI of the difference -5.7 to 10.8). CONCLUSIONS: Patients with acute exacerbations of COPD uncomplicated by acidotic respiratory failure or other medical problems can be discharged home earlier than is current practice with support by visiting respiratory nurses. No difference was found in the subsequent need for readmission.     

A phase I trial of the dual farnesyltransferase and geranylgeranyltransferase inhibitor L-778,123 and radiotherapy for locally advanced pancreatic cancer.

PURPOSE: Preclinical and clinical studies have demonstrated that inhibition of prenylation can radiosensitize cell lines with activation of Ras and produce clinical response in patients with cancer. The aim of this study was to determine the maximally tolerated dose of the dual farnesyltransferase and geranylgeranyltransferase I inhibitor L-778,123 in combination with radiotherapy for patients with locally advanced pancreatic cancer. EXPERIMENTAL DESIGN: L-778,123 was given by continuous intravenous infusion with concomitant radiotherapy to 59.4 Gy in standard fractions. Two L-778,123 dose levels were tested: 280 mg/m2/day over weeks 1, 2, 4, and 5 for dose level 1; and 560 mg/m2/day over weeks 1, 2, 4, 5, and 7 for dose level 2. RESULTS: There were no dose-limiting toxicities observed in the eight patients treated on dose level 1. Two of the four patients on dose level 2 experienced dose-limiting toxicities consisting of grade 3 diarrhea in one case and grade 3 gastrointestinal hemorrhage associated with grade 3 thrombocytopenia and neutropenia in the other case. Other common toxicities were mild neutropenia, dehydration, hyperglycemia, and nausea/vomiting. One patient on dose level 1 showed a partial response of 6 months in duration. Both reversible inhibition of HDJ2 farnesylation and radiosensitization of a study patient-derived cell line were demonstrated in the presence of L-778,123. K-RAS mutations were found in three of the four patients evaluated. CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed.     

Longitudinal neurological follow-up of a group of HIV-seropositive and HIV-seronegative hemophiliacs: results from the hemophilia growth and development study

BACKGROUND: Boys and young men with hemophilia treated with factor infusions before 1985 had a substantial risk of acquiring the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome. This study was designed to assess the effects of HIV and hemophilia per se on neurological function in a large cohort of subjects with hemophilia, and to investigate the relationships between neurological disease and death during follow-up. METHODS: Three hundred thirty-three boys and young men (207 HIV seropositive and 126 HIV seronegative) were evaluated longitudinally in a multicenter, multidisciplinary study. Neurological history and examination were conducted at baseline and annually for 4 years. The relationship between neurological variables, HIV serostatus, CD4+ cell counts, and vital status at the conclusion of the study was examined using logistic regression models. RESULTS: The risks of nonhemophilia-associated muscle atrophy, behavior change, and gait disturbance increased with time in immune compromised HIV-seropositive subjects compared with HIV seronegative or immunologically stable HIV-seropositive subjects. The risk of behavior change in immune compromised HIV-seropositive hemophiliacs, for example, rose to 60% by year 4 versus 10% to 17% for the other study groups. Forty-five subjects (13.5%), all of whom were HIV seropositive, died by year 4. Subjects who died had had increased risks of hyperreflexia, nonhemophilia-associated muscle atrophy, and behavior change. CONCLUSIONS: These results indicate that immune compromised, HIV-seropositive hemophiliacs have high rates of neurological abnormalities over time and that neurological abnormalities were common among subjects who later died. By contrast, immunologically stable HIV-seropositive subjects did not differ from the HIV-seronegative participants. Hemophilia per se was associated with progressive abnormalities of gait, coordination, and motor function.     

Hormone replacement therapy with dydrogesterone and 17β-oestradiol: effects on serum lipoproteins and glucose tolerance during 24 month follow up

Objective To assess serum lipid and lipoprotein concentrations and oral glucose tolerance in postmenopausal women treated with 17β-oestradiol (2 mg/day) and cyclical dydrogesterone (10 mg/day for 14 days per 28 day cycle).
Design A 24 month prospective study of 29 women acting as their own controls. On-treatment samples were taken during the combined (oestrogen–progestogen) phase of therapy.
Setting Metabolic research unit in London.
Population Postmenopausal women with no previous exposure to hormone replacement therapy attending a menopause clinic in a London hospital.
Methods Fasting serum sampling and oral glucose tolerance testing.
Main outcome measures Serum lipids and lipoprotein concentrations and plasma glucose, insulin and C-peptide responses to an oral glucose load.
Results Restricting the analysis to the 17 women who completed the study, no effect was seen on serum triglyceride concentrations. There was a mean fall of 5.9% (95% CI 1.2 to −13.0) in concentrations of serum total cholesterol, reflecting the balance of a 10.7% fall (95% CI 4.3 to −25.8) in low density lipoprotein cholesterol concentrations and a 16.3% increase (95% CI 7.3 to −25.3) in those of high density lipoproteins. Fasting glucose concentrations and glucose tolerance test responses were unchanged. Fasting insulin concentrations fell substantially (–41.6%, 95% CI −23.4 to −59.8) with falls also being seen in insulin responses to glucose. Fasting C-peptide concentrations increased by 36.2% (95% CI 9.17 to 63.3), with no consistent effect on C-peptide responses to glucose.
Conclusions Dydrogesterone did not appear to oppose the potentially beneficial effects of oestradiol on insulin or either low or high density lipoproteins, making the combination with 17β-oestradiol a potentially useful option for postmenopausal women particularly those at risk of cardiovascular disease or diabetes mellitus.