Biomedical subjects
Publications and source records attributed to H Jenkins.
Cochlear implant surgery by a group of experienced surgeons proceeded without major complications. Computed tomography scans tended to underestimate cochlear obstruction, but a drill-out was infrequently required if the scan was apparently normal.
Monoclonal antibodies linked to paramagnetic immunobeads (Dynabeads) have been used to investigate the distribution of lamin B3 in fractions of Xenopus egg extracts. Lamin B3 behaved as if it were completely soluble and did not co-precipitate with membrane fractions. Sperm pronuclei assembled in lamin depleted egg extracts were compared to pronuclei assembled in mock depleted extracts by field emission in-lens electron scanning microscopy (FEISEM). This technique revealed that the surface structures of the nuclear envelopes, including nuclear pores, appeared to be identical, indicating that lamin depletion does not affect nuclear envelope assembly. One-dimensional and two-dimensional gel electrophoresis was used to analyze soluble proteins co-precipitated with lamin B3 on Dynabeads. Our results indicate that two major species (molecular mass: 105 kDa and 57 kDa) specifically co-precipitate with lamin B3 as well as several minor species. At least three proteins which co-precipitate with lamin B3 were identified as nuclear matrix proteins. Lamin B3 was separated from these proteins and re-inoculated into lamin depleted extracts. This resulted in partial rescue of both lamina assembly and DNA replication. These results imply that lamin B3 is directly involved in the assembly of structures required for the initiation of DNA replication.
PURPOSE: The aim of our investigation was to evaluate the clinical presentation of patients with carcinoid tumors of the colon and to estimate the survival and potential prognostic factors of this tumor type. METHODS: A population-based study was performed using data from the Alberta Cancer Registry between 1964 and 1988 (inclusive). The clinical records and the pathologic material of eligible patients were reviewed. Survival was estimated both as crude survival and with the Kaplan-Meier method. RESULTS: During the 25-year study period (1964-1988), 36 true carcinoid tumors of the colon were diagnosed in Alberta. Carcinoids of the ileocecal region and of the rectum were excluded from the study. The average age at time of diagnosis was 68.4 years; there were 20 males and 16 females. Symptoms (abdominal pain, diarrhea, weakness, anorexia) occurred late in the course of the disease: 64 percent of the lesions were in Dukes D stage and 22 percent were Dukes C at diagnosis. Only one patient presented with a malignant carcinoid syndrome. Lesions occurred most frequently in the cecum (39 percent), followed by transverse and sigmoid colon. Most of the patients were managed surgically. The perioperative mortality rate was with 22 percent, which is quite high. The average size of the lesions was 5.8 (range, 2-10) cm, and most tumors (31/36) had invaded the pericolic fat. The most common immunohistochemical pattern was argentaffin/argyrophil negative and neuron-specific enolase positive. Two-year and five-year actuarial (Kaplan-Meier) survival was 34 percent and 26 percent, respectively. Survival for carcinoids of the colon was significantly lower compared with carcinoids of the rectum or appendix, and with colon adenocarcinomas. Size of the tumor and tumor invasion into the muscularis propria--the two major histopathologic prognostic factors for carcinoids of the gastrointestinal tract--were not found to influence survival significantly. Rather, tumor stage, histologic pattern, tumor differentiation, nuclear grade, and mitotic rate were found to significantly influence the survival rate. CONCLUSION: Carcinoid tumors of the colon are extremely rare tumors, diagnosed late in the course of the disease, and they carry a bad prognosis. Prognostic factors are tumor stage, histologic pattern, differentiation, nuclear grade, and mitotic rate of the tumor.
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It has been reported that somatostatin may be an effective antisecretory agent in a range of conditions causing severe secretory diarrhoea. In many children, intractable diarrhoeal illnesses result in significant morbidity and mortality. In a group of seven children with secretory diarrhoea, the effect of i.v. infusion of somatostatin (3.5 micrograms/kg stratum plus 3.5 micrograms/kg/h) on the net mucosal flux of salt and water was assessed using an in vivo steady-state perfusion technique. In one of the seven children who had evidence of deranged mucosal secretion and preserved villus function, somatostatin infusion resulted in a moderate reduction in secretion. In the remaining six, it had little or no beneficial effect. Somatostatin did not alter the rate of glucose absorption.
Routine biochemical monitoring of parenterally fed newborn infants revealed plasma chloride levels which were higher than widely quoted reference ranges. The parenteral nutrition solutions were reformulated to reduce the chloride infusion rate. In a historically controlled study, 28 infants receiving the original formulation were compared with 31 infants receiving the new formulation. The mean plasma chloride level was 4.8 mmol/l lower in the new formulation group than in the original formulation group (95% confidence interval 2.5-7.2 mmol/l). The mean base excess level was 3.1 mmol/l higher in the new formulation group than in the original formulation group (95% confidence interval 1.9-4.8 mmol/l). A reduction in the chloride load by using acetate salts can be safely achieved and may decrease the plasma chloride levels and decrease acidosis during the first seven days of life.
A telephone questionnaire was undertaken to evaluate the knowledge of resident paediatricians on the subject of the basic resuscitation of the acutely sick child. The questionnaire was targeted at 88 resident paediatricians in hospitals accepting paediatric emergencies in four health regions. Outcome was measured as a correct response to questions based on several emergency scenarios and on the confidence expressed of basic resuscitation knowledge. The subject of emergency management of the child with a compromised upper airway was poorly answered with 40/73 (55%) resident paediatricians suggesting an incorrect endotracheal tube size for an 8 year old child. Fluid management was also deemed unsatisfactory with only 36/73 (49%) providing adequate transfusion secondary to haemorrhagic shock. In addition only 19/73 (26%) mentioned the intraosseous route as a means of obtaining vascular access in a child in extremis. Confidence of the knowledge of basic resuscitation of children was low among resident paediatricians with only 30/73 (41%) expressing confidence and 69/73 (94%) expressing a desire for more formal training in paediatric resuscitation. Resident paediatricians are usually the key personnel in the management of very sick children. This survey demonstrates a low level of basic resuscitation knowledge among resident paediatricians of all grades that must be remedied at a local and national level.
Xenopus egg extracts, which support nuclear assembly and DNA replication in vitro, were physically depleted of lamin B3 using monoclonal antibodies linked to magnetic beads. Depleted extracts were still able to support nuclear envelope assembly around demembranated sperm heads but the resulting pronuclei lacked a lamina and were unable to initiate semiconservative DNA replication or to assemble replicases, confirming previous data. Immunoblotting analysis of isolated nuclei and nuclear matrix fractions indicated that lamin-depleted nuclei still accumulated nucleoporins and PCNA. Furthermore, the rate of PCNA uptake was identical in lamin-depleted and control nuclei. However, neither the nucleoporins nor the PCNA was associated with nuclear matrix fractions. The major protein components of sperm pronuclear matrix fractions were characterized by two-dimensional gel electrophoresis. Of these proteins only three out of 22 species, other than the lamins, were significantly reduced in lamin-depleted nuclei, indicating that these nuclei do assemble a nuclear matrix.
The stage at diagnosis and the survival experience of 41 women who developed breast cancer after cosmetic breast augmentation were compared with those of all other patients with breast cancer (n = 13,246) diagnosed in Alberta from 1973 to 1990 (inclusive). The tumors in women with breast implants were smaller (65.9 percent < or = 2 cm) as compared with the tumors in women without implants (34.1 percent < or = 2 cm), but lymph node and distant metastases were equally frequent in the two groups. The distribution of tumor histologic types did not differ significantly between women with or without implants. Women who had an implant were younger at diagnosis of breast cancer compared with women with breast cancer and no breast implants. The relative 5- and 10-year survival rates did not differ significantly between the two groups, and the Kaplan-Meier survival estimate also was similar. It is concluded that women with breast implants in whom breast cancer develops are not diagnosed in a later stage and do not experience an impaired survival as compared with breast cancer patients without implants.
BACKGROUND: A relation between breast augmentation and the subsequent risk of breast cancer has been postulated. Since an estimated 2 million women in the United States alone have received breast implants, even a small increase in the risk of breast cancer could have considerable public health consequences. METHODS: We performed a population-based nonconcurrent cohort-linkage study. All women in Alberta, Canada, who underwent cosmetic breast augmentation from 1973 through 1986 were included in the implant cohort (n = 11,676). This cohort was compared with the cohort of all women in Alberta in whom a first primary breast cancer was diagnosed (n = 13,557). The expected number of breast-cancer cases in the implant cohort was estimated by applying age-specific and calendar year--specific incidence rates of breast cancer (obtained from the Alberta Cancer Registry) to the implant cohort. Standardized incidence ratios were calculated by dividing the observed by the expected number of breast-cancer cases in the implant cohort. RESULTS: Forty-one patients with implants were subsequently found to have breast cancer. The expected number was 86.2. The standardized incidence ratio was thus 47.6 percent, significantly lower than expected (P less than 0.01). The average length of follow-up in the implant cohort was 10.2 years, and the average length of time from breast augmentation to the diagnosis of breast cancer was 7.5 years. CONCLUSIONS: Women who undergo breast augmentation with silicone implants have a lower risk of breast cancer than the general population. This finding suggests that these women are drawn from a population already at low risk and that the implants do not substantially increase the risk.
We have identified a candidate for the gene responsible for multiple endocrine neoplasia type 2A (MEN 2A) at D10S94 in proximal 10q11.2. An evolutionarily conserved sequence from D10S94 was used as a probe to isolate cDNAs corresponding to a gene that we have termed mcs94-1. The gene spans 11 kb and has an unmethylated CpG island at its 5' end. The mcs94-1 transcript is approximately 2.4 kb in length and is widely expressed. It encodes a putative 415-amino-acid polypeptide that is similar in sequence to nucleolin, an abundant nucleolar protein. Mcs94-1 was examined as a candidate for MEN2A through nucleotide sequence analysis of mcs94-1 exons from an MEN 2A chromosome and its wildtype homologue from an MEN 2A patient. The major portion of the expressed mcs94-1 sequence was examined. No differences in sequence were found between the two alleles.
Drawing upon the comprehensive population-based Northern Alberta Breast Cancer Registry containing 704 patients with histologically negative axillary lymph nodes who have been followed for 5-16 years, we have undertaken a retrospective case-control study to evaluate the utility of genomic amplification of specific protooncogenes [c-erbB-2 (nee HER-2/neu), c-erbA, c-myc, int-2, and hst-1] as predictive indicators of clinical outcome in node-negative disease. To this end, 115 women with node-negative breast cancer who had recurred at any time up to 16 years posttreatment (cases) were matched pairwise for appropriate clinicopathological variables (size of primary tumor, menopausal state, estrogen receptor status, anniversary year of treatment, and patient age) with a second group of 115 women (controls) selected from a cohort of 502 node-negative patients who had not relapsed during long-term follow-up. Tumor DNA extracted from archival formalin-fixed, paraffin-embedded tissue blocks were analyzed for protooncogene copy number by slot-blot hybridization. Taking a gene copy number of 3 as the cutoff, 27 of the 230 tumor samples examined contained from 3- to 22-fold elevation in c-erbB-2 genomic equivalents. Twenty-one of the 27 tumors amplified for c-erbB-2 were derived from cases and 6 from controls, signifying that 18% of the node-negative patients who had relapsed harbored excessive copies of the protooncogene in their malignant tissue compared to only 5% for the patients who had remained in remission. Accordingly, the occurrence of amplification of c-erbB-2 proved to be a statistically significant predictor of poor prognosis, especially disease-free interval (P = 0.006). Moreover, this genetic alteration appeared to be independent of and to have greater predictive power than most commonly used prognostic factors. Our findings also indicated that as a clinical test, measurement of c-erbB-2 amplification suffers from low sensitivity; however, when greater than 6 gene copies are present, the test has a positive predictive value for recurrence of 70%. Concurrent analysis of tumor DNA blots with probes for the other four protooncogenes examined revealed that their amplification, which others have reported to arise often, especially in node-positive disease, was seldom found even in our high-risk case group (2-3%). In short, our data strongly suggest that amplification of c-erbB-2 may contribute to the pathogenesis of some forms of node-negative breast cancer and thus may serve as a useful genetic marker to identify a subset of high-risk patients.
The enantiomers of 2-[2-(dimethylamino)ethyl]-3,4-dihydro-4-methylpyrido[3,2-f]-1,4- oxazapine-5(2H)-thione (rocastine) and two of its more potent analogues were prepared with an enantiomeric purity of greater than 99.9%. The antihistaminic activity of these compounds was assessed by their ability to block histamine-induced lethality in guinea pigs and to inhibit [3H]mepyramine binding to guinea pig cortex. In this series, compounds having the R configuration at the 2-position are at least 300 times more potent than the S isomers. Conformational analysis and molecular modeling suggest that rocastine can adopt a conformation in which the pyridine ring, ether oxygen, and protonated amine functions are positioned similarly to the corresponding elements of the probable binding conformers of some of the more classical antihistamines. This conformation, boatlike in the oxazepine ring with the side chain quasi-equatorial and folded back toward the ring, is the likely binding conformer at the histamine H1 receptor, and the available structure-activity relationship data is consistent with this interpretation.
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In order to obtain a more correct estimate of cancer incidence in relatives of cases with ovarian cancer and relatives of age-matched controls, information was obtained on family size, date of birth and death, and cancer history. The average total number of first degree (parents and siblings) and some second degree (uncles and aunts) relatives for cases (15.03) and controls (15.22) is very similar. Of all the relatives 33% were Alberta residents or decreased in Alberta after 1966 so they could be checked in the population based Alberta Cancer Registry. There was a 14% level of error in the information provided, 9% for first degree relatives and 25% for uncles and aunts. The errors included missed malignancies, benign lesions quoted as malignancies, incorrect cancer site and inaccurate dates of birth, diagnosis or death. Results were compared between the relatives of cases and controls using either all relatives or only Alberta residents. For the Alberta residents, expected numbers of malignancies were calculated by age/sex-specific person/years and age/sex-specific incidence rates. The number of relatives with ovarian cancer is significantly higher in cases than in controls in both data sets, but shows a limited relative risk of 2.61 (95% confidence limits 1.12-1.59). Clustering of cases is exceptional, only one patient out of 197 had two relatives with ovarian cancer and this was a case with a larger than average total number of relatives. In conclusion, although there is a significantly higher incidence of ovarian cancer in the family history of cases than of controls, it is not very common and only nine out of 197 cases (4.6%) presented with such background.
Individual speech tracking data were analyzed in relation to other variables in 11 adult users of the Nucleus multichannel cochlear implant. Patients were categorized according to postoperative speech tracking results. The resultant groups could also be differentiated on the basis of postoperative MAC scores, surgeon's rating of overall success, and duration of deafness before implantation. The speech tracking paradigm appears to be a useful technique for the evaluation of performance with a cochlear prosthesis.
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