Follow-up after curative treatment for colorectal cancer: longitudinal evaluation of patient initiated follow-up in the first 12 months.

PURPOSE: To compare patient-triggered follow-up (PTFU) for curatively treated colorectal cancer against traditional outpatient follow-up (OPFU). METHODS: Questionnaires were mailed at four time points over one-year post-treatment to two prospectively-recruited cohorts: A, patients entering follow-up and receiving OPFU pre-implementation of PTFU; B, patients entering follow-up (FU) and receiving either OPFU (B1) or PTFU (B2) post-implementation of PTFU. Bi-variate tests were used to compare patient characteristics and outcomes eight months after entering follow-up (generic and cancer-specific quality of life (QoL), satisfaction). Regression analysis explored associations between follow-up model and outcomes. Resource implications and costs of models were compared. RESULTS: Patients in Cohort B1 were significantly more likely to have received chemotherapy (p < 0.001), radiotherapy (p < 0.05), and reported poorer QoL (p = 0.001). Having a longstanding co-morbid condition was the most important determinant of QoL (p < 0.001); model of care was not significant. Patients were satisfied with their follow-up care regardless of model. Health service costs were higher in PTFU over the first year CONCLUSIONS: PTFU is acceptable to patients with colorectal cancer and can be considered to be a realistic alternative to OPFU for clinically suitable patients. The initial costs are higher due to provision of a self-management (SM) programme and remote surveillance. Further research is needed to establish long-term outcomes and costs.

Agency-offered and officer-utilized suicide prevention and wellness programs: A national study.

Limited research exists in the area of police mental wellness and suicide prevention, especially regarding programs utilized by these agencies. The purpose of this project was to gain a better understanding of the prevalence of use of police officer wellness promotion and suicide prevention programs implemented in the United States and an understanding of the perceptions of program effectiveness (Part A). We also sought to determine whether differences exist in the mental wellness and perspectives of programming of officers from agencies who utilize suicide prevention and wellness programs compared to those agencies who do not (Part B). Data for Part A was collected directly from agencies via a stratified random sample of city police departments and sheriff's offices nationwide. Part B entailed completion of online surveys by individual officers from agencies participating in Part A. The final sample included 55 agencies for Part A and 144 officers for Part B. At the agency level (Part A), Employee Assistance Programs or counseling services were the most common programs offered, and, notably, planning for programming was inconsistent or not well established. At the officer level (Part B), almost 25% of respondents did not know whether their agency had programming; 35% did not feel their agency supports its officers' mental wellness. For officers who did feel their wellness was supported, they reported significantly less stress and higher overall well-being. Of officer respondents, 12.4% indicated it was either "quite" or "very likely" they would attempt suicide someday. Implications and suggestions for law enforcement agencies are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Comparison of oral glucose tolerance tests and mixed meals in patients with apparent idiopathic postabsorptive hypoglycemia: absence of hypoglycemia after meals.

The relationship between symptoms of idiopathic postabsorptive hypoglycemia and glucose homeostasis was evaluated by giving oral glucose tolerance tests (OGTT) and mixed meals to 18 patients and 16 controls. Chemical hypoglycemia after OGTT occurred as often in patients referred because of possible hypoglycemia symptoms, 18 out of 80 (23%), as in controls, 4 out of 16 (25%). After glucose, patients showed both clinical and chemical hypoglycemia (mean +/- SE plasma glucose, 48 +/- 3 mg/dl), but insulin, glucagon, and growth hormone responses were similar to controls. After mixed meals, no chemical hypoglycemia occurred in patients (mean plasma glucose, 79 +/- 3 mg/dl), yet 14 out of 18 (78%) had symptoms and/or signs consistent with hypoglycemia. No abnormality of glucose homeostasis was observed after meals that could account for symptoms or signs experienced by patients with idiopathic postabsorptive hypoglycemia. Since factors other than hypoglycemia appear to be involved, the disorder should be termed the idiopathic postprandial syndrome to avoid the connotation of chemical hypoglycemia.

Radioiodine-induced thyroid storm. Case report and literature review.

Thyroid storm developed following radioiodine therapy in a 43-year-old man with Graves' disease, weight loss, myopathy, severe thyrotoxic hypercalcemia, and a pituitary adenoma. The hypercalcemia may have been a significant, and previously unreported, predisposing factor for the radioiodine-associated thyroid storm. This case and 15 other well-documented cases of radioiodine-associated storm found in the literature are reviewed, as are several other cases of less severe exacerbations of thyrotoxicosis associated with radioiodine therapy. Although not often seen, these complications are often fatal. High-risk patients, such as the elderly, those with severe thyrotoxicosis, and those with significant underlying diseases, may benefit from preventive measures such as the judicious use of thyrostatic medications during the periods before and after isotope administration.

Serum thyroglobulin levels predict total body iodine scan findings in patients with treated well-differentiated thyroid carcinoma.

Forty-eight consecutive patients with treated thyroid carcinoma were studied with 131-I total body scans and serum thyroglobulin (hTg) levels. Serum hTg levels during thyroxine treatment accurately predicted scan results (chi square = 18.6, p < 0.001). All patients with negative scans (24 patients) had serum hTg levels (< 7 ng/ml whereas in patients with metastatic thyroid cancer (eight patients) they ranged from 11 to 690 ng/ml. In patients with iodine uptake confined to the thyroid bed (16 patients) serum hTg values ranged from 2 to 17 ng/ml. Serum hTg levels rose in patients with negative scans during hypothyroidism or after exogenous TSH suggesting that hTg levels are more sensitive than iodine scans in detecting residual thyroid tissue. Serum hTg levels could replace total body iodine scans in many patients with treated thyroid carcinoma.

Cellular responses to DNA damage.

For many years, the study of the regulation of the SOS network was complicated by both the complexities of the responses and the interrelationships of the key regulatory elements. However, recently the application of powerful genetic and molecular biological techniques has allowed us to gain a detailed picture of the regulation of this complex network. The network is now known to consist of more than 17 genes, each of which is repressed by the LexA protein. Induction of the genes in the SOS network occurs when the RecA protein becomes activated in response to a signal generated by DNA damage. Two of the genes in this network, umuD and umuC, are absolutely required for mutagenesis by UV and various carcinogens. The umuD and umuC genes have molecular weights of 16,000 and 45,000 daltons, respectively, and are organized in an operon repressed by LexA. The mutagenesis-enhancing plasmid pKM101 carries two genes mucA and mucB, which are analogs of the umuD and umuC genes, respectively.

B-lymphocyte associated differentiation antigen expression by 'non-B, non-T' acute lymphoblastic leukemia.

We investigated the neoplastic cells obtained from 37 cases of 'non-B, non-T' (SIg-E-) acute lymphoblastic leukemia (ALL) for their expression of 13 distinct monoclonal antibody defined B lymphocyte associated differentiation antigens. We correlated the expression of these B cell antigens with terminal deoxynucleotidyl transferase (TdT), HLA-DR antigen, common ALL antigen (cALLa), and cytoplasmic mu heavy chain (Cu) expression by these neoplastic cells. In this way, we were able to describe a hierarchy of B lymphocyte associated differentiation antigens as well as the marked phenotypic heterogeneity of 'non-B, non-T' ALL. TdT and HLA-DR are expressed throughout the stages of B cell differentiation represented by 'non-B, non-T' ALL. The earliest B cell antigen appears to be Leu 12 (B4) followed by BA-2 and then BL2. OKB2, BL1 and BA-1 are acquired next, followed by B1, BL3, cALLa and Cu. BL7 appears just prior to SIg. OKB1, OKB4, OKB7 and BL4 appear at or after the time of SIg expression and hence are not expressed by 'non-B, non-T' ALL cells. This developmental hierarchy is supported by the results of phorbol ester (TPA) induction studies. Thus, cases of 'non-B, non-T' ALL constitute a useful model for probing the hierarchal expression of B cell antigens and delineating the B cell developmental pathway(s).

Novel bcl-2 breakpoints in patients with follicular lymphoma.

Using genomic DNA from patients with follicular lymphoma, we performed polymerase chain reaction (PCR) amplifications to detect t(14;18) translocations. Unexpectedly large products of approximately 1 kilobase (kb) were detected by gel electrophoresis in 2 of 50 positive cases. In these 2 cases, sequence analyses showed novel breakpoints in the 3' untranslated region of bcl-2, approximately 800 bp downstream of the major breakpoint region (mbr). The breakpoints in IgH occurred in JH4 in one patient and JH5 in the other. Sequences just upstream of the new bcl-2 breakpoints suggest a mechanism of translocation that may include minisatellite core-mediated recombination. In one of our two patients with novel bcl-2 breakpoints, the approximately 1 kb product obtained using conventional mbr primers was detectable only when a nested PCR was performed. These findings have important implications for diagnosis and minimal residual disease detection in t(14;18)-positive lymphomas.

Randomised blind controlled trial of a high fibre, low fat and low sodium dietary regimen in mild essential hypertension.

Thirty-four patients with essential hypertension were allocated, in a controlled trial, to a treatment diet of high fibre, low fat and low sodium composition, or to a control diet by the hospital dietitian. Clinical observations were made by a separate 'blinded' nursing sister. After three months treatment, the modified diet-treated group showed a significant reduction in mean systolic (169.4 +/- 23.4 to 150.6 +/- 16.1 mmHg) and diastolic blood pressure (101.5 +/- 7.3 to 89.4 +/- 6.8 mmHg), accompanied by significant reductions in urinary sodium excretion (140.4 +/- 34.6 to 93.7 +/- 44 mmol/day) and weight (73.1 +/- 10 to 71.2 +/- 8.4 kg). The changes in control were; systolic 171.2 +/- 14.1 to 162.1 +/- 19.5 mmHg and diastolic pressure 97.2 +/- 10.8 to 91.7 +/- 9.7 mmHg. The mean differences in reductions between treated and control were 8.8 mmHg Systolic (95% confidence intervals: -2.6 to 21.2 mmHg) and 7.0 mmHg diastolic blood pressure (95% confidence intervals: 0.4 to 14.4 mmHg). The number of patients with normal blood pressure in the diet treated group at three months was double that in the control (eleven versus five). No relationships were shown between blood pressure changes and those of weight or urinary sodium excretion during the trial. The findings in this study are broadly in agreement with similar ones in essential hypertension and suggest that this form of dietary regimen has a clinically worthwhile hypotensive effect and this should be readily achievable in routine clinical practice.

Restoration of cerebrovascular responsiveness to hyperventilation by the oxygen radical scavenger n-acetylcysteine following experimental traumatic brain injury.

Previous experiments have shown that, following experimental fluid-percussion brain injury, cyclo-oxygenase-dependent formation of oxygen radicals prevents arteriolar vasoconstriction in response to hyperventilation. The oxygen radical scavengers superoxide dismutase and catalase restore normal reactivity; however, they are not routinely available for clinical use. The present study tested whether n-acetylcysteine (Mucomyst), an agent currently available for acetaminophen toxicity, could be used as a radical scavenger to restore reactivity after brain injury. N-acetylcysteine (163 mg/kg) was given intraperitoneally prior to or 30 minutes after fluid-percussion brain injury (2.6 atm) in cats, and reactivity to hyperventilation was tested 1 hour after injury. The authors found either that pre- or postinjury administration led to normal reactivity. Additional experiments supported the hypothesis that n-acetylcysteine is an oxygen radical scavenger, since it reduced or prevented the free radical-dependent cerebral arteriolar dilation normally induced by the topical application of arachidonic acid or bradykinin. The mechanism by which n-acetylcysteine is effective in trauma may involve direct scavenging of radicals or stimulation of glutathione peroxidase activity. The results suggest that n-acetylcysteine may be useful for treatment of oxygen free radical-mediated brain injury.

Survival and mutagenesis of bacteriophage T7 damaged by methyl methanesulfonate and ethyl methanesulfonate.

We have examined survival and mutagenesis of bacteriophage T7 after exposure to the alkylating agents methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS). It was found that although both alkylating agents caused increased reversion of specific T7 mutations, EMS caused a higher frequency of reversion than did MMS. Exposure of the host cells to ultraviolet light so as to induce the SOS system resulted in increased survival (Weigle reactivation) of T7 phage damaged with either EMS or MMS. However, after SOS induction of the host we did not detect an accompanying increase in mutation frequency measured as either reversion of specific T7 mutants or by generation of mutations in the T7 gene that codes for phage ligase. Neither mutation frequency nor survival of alkylated phage was affected by the umuD,C mutation in the Escherichia coli host nor by the presence of plasmid pKM101. This may mean that the mode of Weigle reactivation that is detected in T7 is not mutagenic in nature.

Hyperthyroidism following hypothyroidism.

Two patients are presented who developed autonomous thyrotoxicosis following a diagnosis of primary hypothyroidism. In one of these patients, antibodies to the TSH receptor were typical of Graves' disease when measured as thyrotropin binding inhibitor immunoglobulins (TBII) and as human thyroid adenylate cyclase stimulating (HTACS) activity, while a needle biopsy of the thyroid gland was consistent with lymphocytic thyroiditis. Twenty-one other reported cases of this unusual sequence found in the literature are reviewed. This occurrence is more common than is generally appreciated.

A randomised controlled trial to evaluate both the role and the optimal fractionation of radiotherapy in the conservative management of early breast cancer.

AIMS: Postoperative radiotherapy is routinely used in early breast cancer employing either 50 Gy in 25 daily fractions (long course) or 40 Gy in 15 daily fractions (short course). The role of radiotherapy and shorter fractionation regimens require validation. MATERIALS AND METHODS: Patients with clinical stage I and II disease were randomised to receive immediate radiotherapy or delayed salvage treatment (no radiotherapy). Patients receiving radiotherapy were further randomised between long (50 Gy in 25 daily fractions) or short (40 Gy in 15 daily fractions) regimens. The primary outcome measure was time to first locoregional relapse. Reported results are at a median follow-up of 16.9 years (interquartile range 15.4-18.8). RESULTS: In total, 707 women were recruited between 1985 and 1992: median age 59 years (range 28-80), 68% postmenopausal, median tumour size 2.0 cm (range 0.12-8.0); 271 patients have relapsed: 110 radiotherapy, 161 no radiotherapy. The site of first relapse was locoregional158 (64%) and distant 87 (36%). There was an estimated 24% reduction in the risk of any competing event (local relapse, distant relapse or death) with radiotherapy (hazard ratio = 0.76; 95% confidence interval 0.65, 0.88). The benefit of radiotherapy treatment for all competing event types was statistically significant (X(Wald)(2) = 36.04, P < 0.001). Immediate radiotherapy reduced the risk of locoregional relapse by 62% (hazard ratio = 0.38; 95% confidence interval 0.27, 0.53), consistent across prognostic subgroups. No differences were seen between either radiotherapy fractionation schedules. CONCLUSIONS: This study confirmed better locoregional control for patients with early breast cancer receiving radiotherapy. A radiotherapy schedule of 40 Gy in 15 daily fractions is an efficient and effective regimen that is at least as good as the international conventional regimen of 50 Gy in 25 daily fractions.

Capacity for postreplication repair correlated with transducibility in Rec- mutants of Bacillus subtilis.

Bacillus subtilis strains deficient in transduction, transformation, or both were examined for the ability to remove pyrimidine dimers and to convert deoxyribonucleic acid newly synthesized after ultraviolet irradiation to high molecular weight. In one strain deficient in both recombination processes, short pieces of deoxyribonucleic acid synthesized after irradiation were not converted to high molecular weight. Two transformable strains deficient in transduction were also deficient in postreplication repair (i.e., joining of newly synthesized DNA fragments), whereas a nontransformable strain that was normal in transduction was proficient in postreplication repair. None of the transformable strains showed deficiencies in repair resynthesis or ligase activity. Our results suggest that some recombinational events may be common to transduction and postreplication repair but not to transformation, emphasizing the difference between these two pathways for genetic exchange.

Postreplication repair of deoxyribonucleic acid and daughter strand exchange in uvr- mutants of Bacillus subtilis.

The fate of pyrimidine dimers in deoxyribonucleic acid (DNA) newly synthesized by Bacillus subtilis after ultraviolet irradiation was monitored by use of a damage-specific endonuclease that introduces single-strand breaks adjacent to nearly all of the dimer sites. Two Uvr- strains, one defective in the initiation of dimer excision and the other defective in a function required for efficient dimer excision, were found to be similar to their wild-type parent in the kinetics and extent of converting low-molecular-weight DNA newly synthesized after ultraviolet irradiation to high molecular weight. In the Uvr- strains large molecules of newly synthesized DNA remained susceptible to nicking by the damage-specific endonuclease even after extended incubation in growth medium, whereas the enzyme-sensitive sites were rapidly removed from both preexisting and newly synthesized DNA in Uvr+ cells. Our results support the hypothesis that postreplication repair in bacteria includes recombination between dimer-containing parental DNA strands and newly synthesized strands.

Two-temperature PCR and heteroduplex detection: application to rapid cystic fibrosis screening.

We describe a rapid two-temperature PCR protocol for amplification of genomic DNA applied to the region of the most common mutation (delta F508) of the cystic fibrosis gene. Amplification products are detected as homo- or heteroduplexes on polyacrylamide gels as previously described. Data using two-temperature PCR show complete concordance with allele-specific hybridization after classical three-temperature PCR in 105 normal, carrier and affected individuals. Clinical application is demonstrated in a family which was uninformative by traditional RFLP linkage analysis. Two-temperature PCR may offer advantages of speed and specificity over three-temperature PCR in many clinical and research applications.

In vitro host cell reactivation of alkylated bacteriophage T7 deoxyribonucleic acid by repair-deficient strains of Escherichia coli.

An in vitro system capable of packaging bacteriophage T7 deoxyribonucleic acid (DNA) into phage heads to form viable phage particles has been used to monitor the biological consequences of DNA dam aged by alkylating agents, and an in vitro DNA replication system has been used to examine the ability of alkylated T7 DNA to serve as template for DNA synthesis. The survival of phage resulting from in vitro packaging of DNA preexposed to various concentrations of methyl methane sulfonate or ethyl methane sulfonate closely paralleled the in vivo situation, in which intact phage were exposed to the alkylating agents. Host factors responsible for survival of alkylated T7 have been examined by using wild-type strains of EScherichia coli and mutants deficient in DNA polymerase I (polA) or 3-methyladenine-DNA glycosylase (tag). For both in vivo and in vitro situations, a deficiency in 3-methyladenine-DNA glycosylase dramatically reduced phage survival relative to that in the wild type, whereas a deficiency in DNA polymerase I had an intermediate effect. Furthermore, when the tag mutant was used as an indicator strain, phage survival was enhanced when alkylated DNA was packaged with extracts prepared from a wild-type strain in place of the tag mutant or by complementing a tag extract with an uninfected tag+ extract, indicating in vitro repair during packaging.

Inducible reactivation of bacteriophage T7 damaged by methyl methanesulfonate or UV light.

We examined the effects of host mutations affecting "SOS"-mediated UV light reactivation on the survival of bacteriophage T7 damaged by UV light or methyl methanesulfonate (MMS). Survival of T7 alkylated with MMS was not affected by the presence of plasmid pKM101 or by a umuC mutation in the host. The survival of UV light-irradiated T7 was similar in umuC+ and umuC strains but was slightly enhanced by the presence of pKM101. When phage survival was determined on host cells preirradiated with a single inducing dose of UV light, these same strains permitted higher survival than that seen with noninduced cells for both UV light- and MMS-damaged phage. The extent of T7 reactivation was approximately proportional to the UV light inducing dose inflicted upon each bacterial strain and was dependent upon phage DNA damage. Enhanced survival of T7 after exposure to UV light or MMS was also observed after thermal induction of a dnaB mutant. Thus, lethal lesions introduced by UV light or MMS are apparently repaired more efficiently when host cells are induced for the SOS cascade, and this inducible reactivation of T7 is umuC+ independent.