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PubMed1978

Use of CEA as an indicator of early recurrence and as a guide to a selected second-look procedure in patients with colorectal cancer.

The usefulness of the CEA as an indicator of recurrence and a guide to selected second-look surgery was evaluated from a retrospective analysis of 358 patients with colorectal cancer and from a prospective experience with 16 patients all of whom had been admitted for second-look surgery because of postoperative elevations of CEA only. Our previous experience had shown that after curative resection the CEA usually returned to normal levels (less than 5 ng/ml) within one month, but became elevated at time of clinically obvious recurrence being very high in patients with liver metastases, but only moderately elevated or normal in patients with local recurrence. All 16 patients had previously had curative resection of colorectal cancer; 13 in the rectum or rectosigmoid and three in the right colon. There were 13 Dukes' C and three Dukes' B cancers. All had been followed clinically and by CEA testing at three monthly intervals and were considered free of disease (NED) at time of CEA elevation. The median disease free interval was 13 months (range 4-57 months) and the median CEA prompting admission for second-look operation was 21 ng/ml (range 10-56 ng/ml). The sites of recurrence were liver in six, lung in two and localized disease in six. Two patients had negative exploration for recurrence and were found to have cholelithiasis only (one of these later died of metastases). Resection for cure was done in seven and palliative resection or biopsy only was done in nine patients. At this time, four patients are NED (12-37 months), five are living with disease (10-16 months) and seven have died of disease (2-12 months). The CEA test provides a method of early detection of recurrence and may permit surgical retrieval in selected patients and earlier initiation of palliation in other patients. The longterm effects in patient salvage remain to be defined.

Adult↗
PubMed1998

Bone density in long term users of depot medroxyprogesterone acetate.

OBJECTIVE: To identify any adverse effect on bone density in long term users of depot medroxyprogesterone acetate (DMPA) for contraception. DESIGN: Cross-sectional measurement of bone density in users with amenorrhoea of more than one year or any woman using DMPA for more than five years. SETTING: Community Family Planning Clinics in Portsmouth and Manchester. POPULATION: One hundred and eighty-five women aged 17-52 years (mean 33.3 years) who had used DMPA for between 1 and 16 years and were attending the clinics for further injections, between August 1994 and August 1996. METHODS: Dual energy X-ray measurement of bone density of femoral neck and lumbar spine, and venous blood sample taken just prior to the next injection of DMPA. MAIN OUTCOME MEASURES: Bone density of femoral neck and lumbar spine and serum oestradiol in relationship to years of DMPA use and duration of amenorrhoea. RESULTS: Most women (n=153) had serum oestradiol levels < 150 pmol/l. Despite this, the mean bone density of the lumbar spine compared with the population mean for women aged 20-59 years gave a Z score (95% CI) of -0.332 (-0.510 to -0.154). There was no significant difference in the mean density of the femoral neck from the normal population mean. CONCLUSION: Despite amenorrhoea and low serum oestradiol, this sample of long term DMPA users had bone density only minimally below the normal population mean. We therefore found no clinically important adverse effect on bone density and therefore no reason to recommend bone conserving measures, such as add-back oestrogen.

Adolescent↗
PubMed1981

Follow-up study of phototreated fullterm newborns.

A follow-up study including examinations made by a paediatrician, an ophthalmologist and a psychologist and complemented with EEG-recordings and a number of laboratory determinations was performed at the age of 3 years on 41 children who had received phototherapy during the first week of life and on 42 control children of the same age. No differences were found in growth, development, social maturity, neurological or ophthalmologic disorders, EEG-recordings or laboratory determinations between both groups. It seems unlikely that phototherapy causes any harmful longterm effects provided that the eyes are shielded.

Brain Diseases↗
PubMed1993

Fate of Nissen fundoplication after 20 years. A clinical, endoscopical, and functional analysis.

Of 46 patients who had Nissen fundoplication for proved gastro-oesophageal reflux, 25 were available for follow up after a median of 20 years, 15 had died of unrelated causes, and six could not be traced. All 25 patients in the follow up study were personally interviewed: 21 consented to an endoscopy, 14 to 24 hour recording of oesophageal pH and manometry, and 15 to radionuclide transit test. Repeat fundoplication for recurrent reflux was performed in two cases during the study. Heartburn and regurgitation were significantly lessened (p < 0.005), but the incidence of dysphagia was slightly increased. Endoscopy showed six of 21 fundic wraps to be defective. Erosive oesophagitis was seen in two patients, and Barrett's oesophagus (histologically confirmed) in one of them and six other patients. Total reflux time was abnormal in four of 14 patients. No patient with an intact fundic wrap seen on endoscopy, only two of seven with Barrett's oesophagus, and one of four with abnormal reflux had oesophagitis. Fundoplication in itself did not affect oesophageal motility or transit, provided that the wrap was intact. It is concluded that Nissen fundoplication gave a reasonably good longterm effect in chronic reflux disease, with the stage of the fundic wrap as the main determinant of outcome.

Adult↗
PubMed1993

Duodenal juice total protein and pancreatic enzyme synthesis, turnover, and secretion in patients after acute pancreatitis.

It is controversial whether acute pancreatitis has longterm effects on pancreatic function. Pancreatic enzyme synthesis, turnover, and secretion were measured in 10 patients in clinical remission who had had one or more (one to six) attacks of acute alcoholic pancreatitis. The studies were done between two and 29 months after the most recent attack. A control group included five patients with no evidence of pancreatic disease. A four hour primed/continuous intravenous infusion of [14C]L-leucine tracer was given with secretin (2 U/kg/h) and cholecystokinin (0.5 U/kg/h) and secreted duodenal juice aspirated. Amylase and trypsin were extracted from duodenal juice by affinity chromatography, permitting measurement of the rate of isotope incorporation into total protein, amylase, and trypsin. The results showed non-parallel changes in enzyme synthesis and turnover with decreases in total enzyme protein and amylase synthesis and turnover but preservation of trypsin synthesis and turnover. The low turnover rates may be ascribed to continuing pancreatic cell malfunction after recovery from acute alcoholic pancreatitis and suggest that the decreased amylase secretion rates are partly a consequence of impaired amylase synthesis and not simply because of loss of pancreatic tissue.

Acute Disease↗
PubMed2006

Intense T cell depletion followed by autologous bone marrow transplantation for severe multiple sclerosis.

BACKGROUND: Certain stem cell transplantation procedures might slow down inflammatory pathology in multiple sclerosis (MS). AIMS: To halt disease progression in aggressive MS by a bone marrow transplantation (BMT) protocol aimed at maximum T cell suppression. METHODS: Autologous BMT was performed in 14 patients with rapid secondary progressive MS (median EDSS score at baseline, 6; median disease duration, five years). To accomplish rigorous T cell ablation, a strong conditioning protocol was chosen--cyclophosphamide, total body irradiation, and antithymocyte globulin. To minimise the possibility of reinfusing mature T cells in the graft, bone marrow, not peripheral blood, was used as the CD34+ stem cell source. RESULTS: Median follow up was 36 months (range, 7-36). Post-transplant haemopoietic recovery was successful in all patients. Early toxicity included Epstein-Barr virus related post-transplantation lymphoproliferative disorder. Longterm effects were development of antithyroid antibodies (three) and myelodysplastic syndrome (one). One patient died of progressive disease five years after transplantation. Treatment failure, defined by EDSS increase sustained for six months or more, was seen in nine patients and stabilisation or improvement in five. Other clinical parameters generally showed the same outcome. No gadolinium enhanced lesions were seen on post-treatment magnetic resonance imaging, in either cerebral or spinal cord scans. However, cerebrospinal fluid oligoclonal bands remained positive in most cases. CONCLUSIONS: This strong immunosuppressive regimen did not prevent clinical progression in patients with aggressive secondary MS. The lack of efficacy, together with some serious side effects, does not favour the use of similar rigorous T cell depleting protocols in the future.

Adult↗
PubMed2006

Role of common human TRIM5alpha variants in HIV-1 disease progression.

BACKGROUND: The retroviral restriction factor tripartite motif protein (TRIM)5alpha, is characterized by marked amino acid diversity among primates, including specific clusters of residues under positive selection. The identification of multiple non-synonymous changes in humans suggests that TRIM5alpha variants might be relevant to retroviral pathogenesis. Previous studies have shown that such variants are unlikely to modify susceptibility to HIV-1 infection, or the course of early infection. However, the longterm effect of carrying Trim5alpha variants on disease progression in individuals infected with HIV-1 has not previously been investigated. METHODS: In a cohort of 979 untreated individuals infected with HIV-1 with median follow up 3.2 years and 9,828 CD4 T cell measurements, we analysed common amino acid variations: H43Y, V112F, R136Q, G249D, and H419Y. The rate of CD4 T cell decline before treatment was used as the phenotype. In addition, we extended previous work on the in vitro susceptibility of purified donor CD4 T cells (n = 125) to HIV-1 infection, and on the susceptibility of HeLa cells that were stably transduced with the different TRIM5 variants. Haplotypes were analysed according to the most parsimonious evolutionary structure, where two main human TRIM5alpha groups can be defined according to the residue at amino acid 136. Humans present both Q136 and R136 at similar frequency, and additional TRIM5alpha amino acid variants are almost exclusively derived from R136-carrying haplotypes. RESULTS: We observed modest differences in disease progression for evolutionary branches carrying R136-derived haplotypes, and with the non-synonymous polymorphisms G249D and H419Y. In vitro analysis of susceptibility of donor CD4 T cells, and of the various transduced HeLa cell lines supported the absence of significant differential restriction of HIV-1 infection by the various huTRIM5alpha alleles. CONCLUSION: Common human variants of TRIM5alpha have no effect or modest effect on HIV-1 disease progression. These variants occur at sites conserved throughout evolution, and are remote from clusters of positive selection in the primate lineage. The evolutionary value of the substitutions remains unclear.

Adult↗
PubMed2001

Health of human and livestock conceived by assisted reproduction.

Assisted reproduction is used to resolve infertility problems in human and in breeding programs to generate livestock. Except for gestation length and birth weight, perinatal outcome of children conceived by In Vitro Fertilization is similar to that of spontaneously conceived children. However, large offspring syndrome observed after In Vitro Production in livestock is quite alarming. The distinct parts of assisted reproduction (oocyte maturation, fertilization and culture) have been found to contribute to abnormal fetal growth and development. Genomic imprinting is suggested to be involved in the induction of the aberrant phenotypes observed after assisted reproduction. Furthermore, current knowledge on postnatal health of offspring conceived by assisted reproduction and speculations on potential longterm effects of In Vitro Fertilization will be described.

Animals↗
PubMed1983

Blood and milk concentrations of metronidazole in mothers and infants.

In order to assess the amounts of metronidazole and its clearance in suckling neonates whose mothers received the drug in therapeutic doses, we measured its levels in maternal plasma and milk and in infant plasma. Eleven mothers receiving 600 mg metronidazole daily and 4 receiving 1200 mg and their 15 infants had milk and plasma levels determined with a specific semi-micro high-pressure liquid chromatographic method. Maternal mean plasma levels were 5.0 micrograms/ml, range 1.0 - 11.6 micrograms/ml (600 mg/day) and 12.5 micrograms/ml range 3.7 - 17.9 micrograms/ml (1200 mg/day) and corresponding infant plasma levels were 0.8 micrograms/ml, range 0.3 - 1.4 micrograms/ml and 2.4 micrograms/ml, range 0.6 - 4.9 micrograms/ml. Maternal milk/plasma ratio was 1 and baby/mother plasma ratio was 0.15, independent of dosage (Tab. I). The levels of metronidazole hydroxy metabolite (I) were all below those of metronidazole (Tab. II). Simultaneous milk and blood samples showed almost identical levels (Tab. III). Infant total clearance of metronidazole was calculated to be ca. 60% of maternal clearance by body weight and 24% by body surface, independent of dosage, while maximum infant metronidazole intake was estimated to be 3.0 mg/kg/day assuming a daily intake of 500 ml milk. It is recommended to avoid simultaneous breastfeeding and metronidazole therapy until possible harmful longterm effects on the neonates are known.

Breast Feeding↗
PubMedDate not supplied

Acidification-neutralization processes in a lignite mine spoil amended with fly ash or limestone.

A laboratory experiment was conducted to investigate the longterm effects of amending sulfide-rich lignite mine spoil with fly ash (originating from a coal-fired power station and largely comprised of aluminosilicates) and/or agricultural limestone. The experiment was carried out with soil moisture maintained at field capacity or alternate cycles of wetting and drying. Results obtained suggest that the principal acidification processes were oxidation of sulfide and formation of hydroxysulfate (FeOHSO4), whereas the main neutralization processes were weathering of aluminosilicates in fly ash-treated samples and dissolution of calcium carbonate in limestone-treated samples. The highest dose of limestone rapidly raised the pH of the spoil, but this increase was not maintained throughout the one-year experiment. In contrast, fly ash-treated samples showed a more sustained increase in pH, attributable to the gradual weathering of aluminosilicates. The best results (i.e., good short- and long-term neutralization) were obtained in samples treated with both fly ash and limestone. The low liming capacity of the fly ash (47.85 cmol kg(-1)) means that it must be used in large quantities, an advantage in achieving the further aim of disposing of the fly ash.

Agriculture↗
PubMed2004

[Idopathic tigeminal neuralgia--radiofrequency rhizotomy of ganglion Gasseri].

Idiopathic trigeminal neuralgia (ITN), (tic dou-loureux), may be defined as a chronic painfull disorder of the sensory divisions of the trigeminal nerve, with unexplained cause and pathogenesis. The clinical features are characterized by recurrent paroxysmal lancinating pain confined to distribution of one or more branches of the nerve. Radiofrequency rhizotomy (RFR) of ganglion Gasseri is a methode of choise in treatment of ITN. We present the series of 1600 patients suffering from ITN who underwent RFR between 1984 and 2001. Ages ranged from 29 to 88 years, with a mean age of 62 years. Total pain relief immediately after a single radiofrequency lesion was achieved in 1469 (92%) of patients. After one year a recurrence of pain was present in 145 (10%). Age, sex and duration of illness were unrelated to outcome. Patients previously treated by open surgery appeared to receive less benefit from subsequent RFR. Clinical outcome correlated with the degree of sensory deficit created by RFR. Patients acquiring dense deficit demonstrated a reduced risk of recurrence: 203/1129 (18%) of patients with dense sensory loss and 75/258 (29%) of those with a partial deficit developed a recurrence by three years, whereas almost all patients (78/82) without initial sensory loss suffered a recurrence by three years. Serious complications resulting from RFR were infrequent and the most common was the permanent dysesthesia in 9 (0.6%) of patients. Our results suggest that the RFR is an well bearable and effective longterm surgical treatment for ITN, especially for older and poor-risk patients.

Adult↗
PubMed1984

Nontherapeutic opiate addiction in health professionals: a new form of impairment.

Case studies describe a new type of addicted health professional whose opiate abuse originated recreationally . Historically, health professionals have had high rates of opiate addiction, usually viewed as an occupational hazard stemming from access and from self-treatment for pain or stresses of the medical profession. Partly because addiction in health professionals was almost always therapeutic (iatrogenic) or quasi-therapeutic (stress-related), it affected them less severely than it affected heroin addicts, whose drug abuse usually began recreationally . Now, however, because recreational drug abuse has become commonplace at American colleges since the mid-1960s, a majority of young health professionals have histories of abusing drugs and some are becoming non-therapeutically addicted. Six case studies describe this new addict type, showing how the subjects went from heavy soft drug use to opiate addiction, experienced severe longterm effects, were treated by society, and responded to treatment.

Adult↗
PubMed1983

Vasectomy. What are the long-term risks?

Although vasectomy is becoming a popular method of sterilization, the results of animal studies have led to some concern about the association between vasectomy and subsequent atherosclerosis. After review of the available epidemiological data, it is concluded that there is no evidence that vasectomy is deleterious to humans.

Animals↗
PubMed2000

Estrogen and progesterone regulation of human fibroblast-like synoviocyte function in vitro: implications in rheumatoid arthritis.

OBJECTIVE: Despite increasing evidence regarding the significance of sex hormones in rheumatoid arthritis (RA), their etiopathological role and potential longterm effect on joint destruction remain unclear. We hypothesized that estrogen receptors (ER-alpha) are present in fibroblast-like synoviocytes, and 17beta-estradiol can modulate the production and activity of matrix degrading enzymes produced by these cells. Thus, depending on the endocrine balance, fibroblast-like synoviocyte activity can be suppressed or enhanced, leading to amelioration or exacerbation of the disease process, respectively. METHODS: By utilizing an in vitro cartilage invasion model, in combination with the molecular analyses of hormone receptors, matrix metalloproteinases (MMP) and their respective inhibitors, we investigated the effect of hormones (i.e., estrogen and progesterone) on fibroblast-like synoviocyte phenotypic changes, with particular emphasis on their functional interactions with cartilage. RESULTS: Our studies reveal the presence of functional ER-alpha in fibroblast-like synoviocytes. The findings indicate that estrogen exerts a stimulatory effect, while progesterone has an inhibitory effect on the expression of MMP, their tissue inhibitors (TIMP), and enzymatic activity of MMP produced by these cells. Furthermore, transfection of fibroblast-like synoviocytes with the ER-alpha gene resulted in the increased degradation and invasion of cartilage. CONCLUSION: We identified the presence of functional ER-alpha in fibroblast-like synoviocytes. This renders fibroblast-like synoviocytes as target cells for hormonal regulation. The regulatory effect of estrogen is partly targeted to the MMP and their respective inhibitors associated with fibroblast-like synoviocytes. Such studies provide a link between hormonal status and disease activity in RA and open new venues for future therapeutic intervention to combat this debilitating disease.

Adolescent↗
PubMed1975

[Do veterinarians have obligations (author's transl)].

In a brief introductory part the reasons are stated for which reflection on the ethics of livestock husbandry and veterinary medicine is necessary today. A sharp distinction should be made between facts and standards. The veterinarian has a considerable responsibility in defining the attitude of man towards animals. In addition to consultative curative work, the possibilities of prevention require and active approach. As regards the mainly surgical procedures, the opinion or attitude of the veterinarian will have to be determined by his view (a common view of possible) of his responsibility to himself, the owner of the animal and the animal as an individual or species. Because of longterm effects, equal importance should be attached to these three approaches.

Animal Husbandry↗
PubMed1975

[Proceedings: Early mobilization after myocardial infarct--late results].

The longterm effects of early mobilization after myocardial infarction (MI) have been investigated. 122 patients aged under 65 years were reexamined 84.6 +/- 24 weeks after MI. The physical work capacity (PWC) of these men was 22% below the normal value. Patients with angina pectoris after MI had a PWC only 45% of normal. The overwhelming majority (88%) of MI survivors had returned to their jobs by the end of the follow-up period. Of the conventionally treated patients only 70% had returned to work. Age, PWC after MI and psychological status critically influence the rapidity and rate of return to work after MI.

Angina Pectoris↗