Resection of the irradiated esophagus: the impact of lymph node yield on survival.

There is debate surrounding the appropriate threshold for lymph node harvest during esophagectomy in patients with esophageal cancer, specifically for those receiving preoperative radiation. The purpose of this study was to determine the impact of lymph node yield on survival in patients receiving preoperative chemoradiation for esophageal cancer. The National Cancer Database (NCDB) was utilized to identify patients with esophageal cancer that received preoperative radiation. The cohort was divided into patients undergoing minimal (<9) or extensive (≥9) lymph node yield. Demographic, operative, and postoperative outcomes were compared between the groups. Kaplan-Meier analysis with the log rank test was used to compare survival between the yield groups. Cox proportional hazards model was used to determine the association between lymph node yield and survival. In total, 886 cases were included: 349 (39%) belonging to the minimal node group and 537 (61%) to the extensive group. Unadjusted 5-year survival was similar between the minimal and extensive groups, respectively (37.3% vs. 38.8%; P > 0.05). After adjustment using Cox regression, extensive lymph node yield was associated with survival (hazard ratio 0.80, confidence interval 0.66-0.98, P = 0.03). This study suggests that extensive lymph node yield is advantageous for patients with esophageal cancer undergoing esophagectomy following induction therapy. This most likely reflects improved diagnosis and staging with extensive yield.

Disparities in colostomy reversal after Hartmann's procedure for diverticulitis.

BACKGROUND: Hartmann's procedure for diverticulitis is a common procedure, with highly variable rates and timing of colostomy reversal. The aim of this study was to evaluate the impact of race and insurance coverage on reversal within 2 years of Hartmann's procedure for diverticulitis. METHODS: The Healthcare Cost and Utilization Project (HCUP) State Inpatient Database of five states (2007-2010) was queried for patients who had Hartmann's procedure in the setting of diverticulitis. Patients were grouped by race and insurance status, and multivariable adjustment was performed to evaluate rate and timing of colostomy takedown at 2 years. RESULTS: Among 11,019 patients who had Hartmann's procedure for diverticulitis, 6900 (69%) patients had colostomy reversal by 2 years, with a median time to reversal of 19 weeks. Compared to white patients with private insurance, combinations of black race and non-private insurance significantly reduced likelihood of colostomy reversal at 2 years across all combinations. Black patients without insurance had the lowest likelihood of reversal at 2 years (OR 0.27, 95% CI 0.14-0.51, p < 0.001). For patients who had colostomy reversal within 2 years, black patients without insurance had a significant delay in time to reversal (11 weeks, 95% CI 6-16, p < 0.001) compared to white patients with private insurance, and delays persisted across all other groups. CONCLUSIONS: Black patients and those without private insurance experienced significantly lower rates of, and delayed time to, colostomy reversal compared to white patients with private insurance. These disparities must be considered for allocation of resources in marginalized communities.

Transglutaminase 1-deficient recessive lamellar ichthyosis associated with a LINE-1 insertion in Jack Russell terrier dogs.

BACKGROUND: Congenital, nonepidermolytic cornification disorders phenotypically resembling human autosomal recessive ichthyosis have been described in purebred dog breeds, including Jack Russell terrier (JRT) dogs. One cause of gene mutation important to humans and dogs is transposon insertions. OBJECTIVES: To describe an autosomal recessive, severe nonepidermolytic ichthyosis resembling lamellar ichthyosis (LI) in JRT dogs due to insertion of a long interspersed nucleotide element (LINE-1) in the transglutaminase 1 (TGM1) gene. METHODS: Dogs were evaluated clinically, and skin samples were examined by light and electron microscopy. Phenotypic information and genotyping with a canine microsatellite marker suggested TGM1 to be a candidate gene. Genomic DNA samples and cDNA generated from epidermal RNA were examined. Consequences of the mutation were evaluated by Western blotting, quantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme activity from cultured keratinocytes. RESULTS: Affected dogs had generalized severe hyperkeratosis. Histological examination defined laminated to compact hyperkeratosis without epidermolysis; ultrastructurally, cornified envelopes were thin. Affected dogs were homozygous for a 1980-bp insertion within intron 9 of TGM1. The sequence of the insertion was that of a canine LINE-1 element. Quantitative RT-PCR indicated a significant decrease in TGM1 mRNA in affected dogs compared with wild-type. TGM1 protein was markedly decreased on immunoblotting, and membrane-associated enzyme activity was diminished in affected dogs. CONCLUSIONS: Based on morphological and molecular features, this disease is homologous with TGM1-deficient LI in humans, clinically models LI better than the genetically modified mouse and represents its first spontaneous animal model. This is the first reported form of LI due to transposon insertion.

Digging up the canine genome--a tale to wag about.

There is incredible morphological and behavioral diversity among the hundreds of breeds of the domestic dog, CANIS FAMILIARIS. Many of these breeds have come into existence within the last few hundred years. While there are obvious phenotypic differences among breeds, there is marked interbreed genetic homogeneity. Thus, study of canine genetics and genomics is of importance to comparative genomics, evolutionary biology and study of human hereditary diseases. The most recent version of the map of the canine genome is comprised of 3,270 markers mapped to 3,021 unique positions with an average intermarker distance of approximately 1 Mb. The markers include approximately 1,600 microsatellite markers, about 1,000 gene-based markers, and almost 700 bacterial artificial chromosome-end markers. Importantly, integration of radiation hybrid and linkage maps has greatly enhanced the utility of the map. Additionally, mapping the genome has led directly to characterization of microsatellite markers ideal for whole genome linkage scans. Thus, workers are now able to exploit the canine genome for a wide variety of genetic studies. Finally, the decision to sequence the canine genome highlights the dog's evolutionary and physiologic position between the mouse and human and its importance as a model for study of mammalian genetics and human hereditary diseases.

Maternal anti-factor Xa activity following subcutaneous unfractionated heparin after Caesarean section.

Unfractionated heparin is widely used for prophylaxis against venous thromboembolism after Caesarean section. We performed a survey of thromboprophylactic methods after elective Caesarean section in 50 maternity units in the United Kingdom. We found that a variety of regimens were used. Thirteen (26%) used subcutaneous unfractionated heparin at standard (non-pregnant) doses. We then studied anti-Xa activity in women following elective Caesarean section under regional anaesthesia. Initially, eight women were given 5000 U unfractionated heparin subcutaneously after surgery and anti-Xa activity was measured 1, 2, 3, 4, 5, 6, 8 and 10 h after administration. There was no detectable anti-Xa activity in any of the samples so the dose was increased to 7500 U in a further five women and a single anti-Xa assay performed at 3 h when peak activity should occur. Again, no activity was detected so the dose was increased to 10 000 U heparin in a final group of 10 women and anti-Xa activity measured at 0.5, 1, 1.5, 2, 3, 4, 5 and 6 h. Although there was some activity after 10 000 U heparin, the level was below that accepted for prophylaxis. If anti-Xa activity is an appropriate monitor of prophylactic unfractionated heparin, doses up to 10 000 U are inadequate. Since there is evidence that enoxaparin is effective at producing adequate prophylactic anti-Xa activity following Caesarean section, we suggest abandoning the use of unfractionated heparin in favour of enoxaparin for this purpose.

Osteoporosis and genetic influence: a three-generation study.

We have studied 27 triads of mother, daughter and grandmother for possible genetic influence on distal and proximal forearm bone density, measured by single photon absorptiometry. We found a significant correlation of bone density at the proximal forearm between the mothers and grandmothers (r = 0.499, P < 0.01). There was also a weak correlation between proximal forearm bone densities of mothers and daughters (r = 0.327, P < 0.1). Significant correlations were found between the three generations for grip strength, pedometry, height and triceps skinfold thickness. There was also significant correlation between mother and grandmother for alcohol intake. There was no correlation for contraceptive pill use, smoking, dietary calcium intake, body weight or body mass index. The study concludes that, although there are similarities in bone mineral content between the three generations, genetic factors cannot be conclusively proven to be the major determinant of bone density. Lifestyle and environmental factors may have a bearing on achieving the peak bone mass and subsequent development of osteoporosis.

Climacteric symptoms in healthy middle-aged women.

The incidence of climacteric symptoms was determined in 247 healthy premenopausal women in a community setting. These volunteers had been recruited to a longitudinal study of bone density. Of these subjects, 46 ceased to menstruate during the study, and in this subgroup symptoms were compared before and after cessation of menstruation. Only hot flushes increased after cessation of menstruation in the longitudinal study and showed age correlation in the cross-sectional study. Hot flushes thus emerged as a true menopausal symptom. Although evidence for this is weaker, cold sweats and suffocation seem likely to be genuinely menopausal. Breast discomfort and the four mood symptoms of irritability, excitability, depression and poor concentration improved after cessation of menstruation, and this study gives no support for their being part of the menopausal syndrome; it suggests that these symptoms are more likely to be related to menstruation than to the menopause.

Determinants of forearm bone density in premenopausal women: a study in one general practice.

Predictors of distal and proximal forearm bone density, measured by photon absorbtiometry, were investigated in 248 premenopausal women aged 39-56 years. Only one strong predictor of lower bone density was found--history of previous fracture at any site (P less than 0.001). Two other factors showed a weaker association with density, but only at the distal site--history of diuretic use showed a positive association (P less than 0.02) whereas alkaline phosphatase level was inversely correlated with density (P less than 0.01). Other factors were not significant predictors: these included age, calcium intake, level of exercise, anthropometric measures of obesity, serum calcium level, parity, lactation history, a menopausal symptom history, use of the contraceptive pill, smoking and alcohol intake. These results contrast with the far stronger predictors found for postmenopausal women and suggest that genetic endowment rather than lifestyle may be the major determinant of bone density before the menopause.

Exercise training-induced alterations of cardiac morphology.

The data to date are ambivalent regarding exercise-induced cardiac enlargement in previously sedentary individuals. The training regimens used in previous longitudinal studies probably did not provide an optimum training stimulus. Accordingly we studied echocardiograms of the left ventricle of 11 relatively inactive individuals pre and post an intense endurance training program, when intensity was increased relative to improvement, thereby providing an optimum training stimulus. Subjects trained 6 days/wk for 7 wk, alternating days of continuous cycling (40 min) and interval running (5 5-min bouts). Exercise intensity was maintained at 85-90% of peak cycle ergometer O2 uptake (VO2) for cycle training by increasing power output approximately 11 W/wk and at approximately 100% of VO2max for run training by increased (P less than 0.01) approximately 950 ml/min (approximately 32%) and was correlated with training duration (r = 0.91; P less than 0.01). Training-induced increases (P less than 0.05) in interventricular septal thickness (IVS, mm) during both systole (13.4 +/- 0.9 to 14.9 +/- 0.8) and diastole (10.4 +/- 0.6 to 11.5 +/- 0.7) and in left ventricular end-diastolic dimension (4.96 +/- 0.16 to 5.13 +/- 0.19 cm). The absolute values of left ventricular end diastolic volume (LVEDV), stroke volume, ejection fraction, and left ventricular mass (LVM) increased (P less than 0.05) after training. Increases (P less than 0.05) in LVEDV index (64.3 +/- 3.3 to 69.0 +/- 3.4 ml/m2) and LVM index (114.1 +/- 6.5 to 124.5 +/- 7.3 g/m2) were also evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Real-time measurement of serum C-reactive protein in the management of infection in the elderly.

The serum concentration of C-reactive protein (CRP), a nonspecific acute phase reactant which responds sensitively to bacterial infection, was measured by homogeneous enzyme immunoassay in all patients admitted to a general hospital geriatric unit. It was then monitored frequently in those in whom infection was suspected. Results were reported rapidly to the clinical team and particularly in the context of a patient population with complex multisystem pathology, often without pyrexia, leucocytosis or other classical signs of infection, they made a significant contribution to patient management. Very high CRP levels were most commonly due to infection (75% of those over 50 mg/l and 94% of those over 100 mg/l) and the pattern of the CRP response during antimicrobial therapy provided a sensitive, objective index of its efficacy. Failure of CRP levels to fall promptly stimulated additional diagnostic investigations, revealing resistant infection, localized pus or serious noninfective pathology, particularly malignancy, and led to appropriate management. Furthermore the CRP results on admission were of considerable prognostic significance, being significantly higher (median 70 mg/l) in those patients who did not survive than in those who did (18 mg/l).

Acute phase protein response to infection in elderly patients.

The presence of infection is often difficult to diagnose in elderly patients. In view of this, laboratory markers of infection are of great clinical importance. The pattern of change in acute phase proteins has not hitherto been studied in elderly patients. In a prospective series of 114 acute elderly admissions to a Geriatric Unit there was a significant change with infection in all proteins studied, but C-reactive protein was the most sensitive marker of the presence and severity of infection and the response to antimicrobial therapy. The best pair of acute phase proteins in the prediction of infection were alpha 1-acid glycoprotein and C-reactive protein whilst albumin and alpha 1-acid glycoprotein together contributed significantly to the prediction of outcome.

Paraplegia and quadriplegia in the elderly due to spinal cord lesions: association with malignancy.

A retrospective study showed that paraplegia and quadriplegia due to spinal cord lesions occurred with a frequency of 1 in 500 admissions to a geriatric department. These cases predominantly were caused by malignant disease, particularly of the bronchus. However, elderly patients presenting to other hospital departments included a far higher proportion of cases with benign causes, particularly cervical spondylosis which affects patients of lower average age. Male patients predominated in both malignant and benign categories.

Proceedings: Female sterilization: long-term follow-up with particular reference to regret.

PIP: 220 women who had been sterilized 20-46 months previously were questioned about any regrets they felt about the operation. 13 patients expressed regret (5.9%) and 15 expressed uncertainty (6.8%). The worsening of the sex life, the occurrence of menorrhagia, dysmenorrhea, or both, and nervous problems were each significantly associated with the regret/uncertain group (p less than .01). 7 patients also experienced weight gain and 3 reported a bad conscience. The percentage of sterilization patients expressing regret is felt likely to decline since smaller families are now favored. The results did not indicate that sterilization necessarily causes the problem.^ieng

Side effects of the pill.

PIP: Recent studies indicate that the urge to reproduce is not an important source of the female libido. The Herzberg et al. studies showed that 19.8% of the women who stopped taking the pill gave loss of libido as the reason; 29.1% gave headache and 27.9% gave depression as their reasons for discontinuing. Women with a predisposition to depression tend to suffer loss of libido with pills and should not have them prescribed. The Herzberg studies showed women with IUDs to have a substantial increase in libido. The Simon Population Trust report of 1969 reported a very high percentage of increased sexual enjoyment after vasectomization and female sterilization.^ieng