Presenting stage and risk group in men dying of prostate cancer.

Introduction: Prostate cancer remains the 3rd leading cause of cancer-related mortality in Canadian men, and yet screening for prostate cancer continues to be controversial because the majority of men diagnosed with prostate cancer do not die of the disease. It also remains uncertain whether treatment of cases that can be treated with curative intent alters the mortality rate. There are very few studies describing the presenting stage, risk groups, and survival after diagnosis for men dying of prostate cancer in the literature. In this study, we explored these characteristics for all men who died of prostate cancer in British Columbia between 2013 and 2015. Methods: The population-based BC Cancer databases were used to identify all patients diagnosed between January 2013 and December 2015 who died of prostate cancer. Patient, tumour, and treatment characteristics were collected, and the risk grouping for each tumour was determined. The proportion of cases in each risk group at the time of diagnosis was determined. Survival time from diagnosis to death was calculated for all patients and for each risk group using the Kaplan-Meier method. Results: A total of 1256 patients died of prostate cancer. Of patients who presented with metastatic disease, 57.2% presented with a Gleason score of 8 or more, compared with only 35.7% of patients who presented with nonmetastatic disease (p < 0.0001). The presenting stage and risk group of those dying of prostate cancer were as follows: 32% metastatic disease, 3% regional (defined as node-positive), 39% localized high risk, 9% localized intermediate risk, 4% localized low risk, 6% localized not otherwise specified, and 7% unknown. Therefore, 80.3% of those with a known risk group presented with either localized high-risk, regional, or metastatic disease at diagnosis. The median survival times from diagnosis to death were 12 years for localized low-risk, 10 years for localized intermediate-risk, 6.5 years for localized high-risk, 4 years for regional, and 1.7 years for metastatic disease at diagnosis. Conclusions: This population-based analysis demonstrates that patients with localized high-risk, regional, or metastatic disease at diagnosis constitute the overwhelming majority of patients who die of prostate cancer in British Columbia. Unless these disease states can reliably be identified at an earlier low- or intermediate-risk localized state in the future, it is unlikely that treatment of localized low- and intermediate-risk cancer will have an impact on survival. Furthermore, patients with de novo metastatic disease had identifiable risk factors of a higher prostate-specific antigen and Gleason score. Further studies are required to confirm these results.

Second-line systemic therapies for metastatic urothelial carcinoma: a population-based cohort analysis.

Introduction: Patients with urothelial carcinoma (uc) have a poor prognosis after progression on first-line cisplatin-based chemotherapy. Real-world data about second-line cytotoxic therapies are limited. We sought to characterize patients with metastatic uc who receive more than 1 line of systemic therapy and to describe their treatments and outcomes. Methods: Using BC Cancer's pharmacy database, we identified patients with documented metastatic uc who had received more than 1 line of systemic therapy. A retrospective chart review was then performed to collect clinicopathologic, treatment, and outcomes data. Results: The 51 included patients, of whom 42 were men (82%), had a median age of 65 years (range: 38-81 years). Sites of metastasis included lymph nodes (n = 30), bone (n = 7), lung (n = 9), and peritoneum (n = 2). Second-line chemotherapy regimens included gemcitabine-cisplatin [gc (n = 14)], paclitaxel (n = 24), docetaxel (n = 12), and an oral topoisomerase i inhibitor (n = 1). Median time to progression (ttp) and overall survival (os) were 2.0 and 6.83 months respectively. Compared with patients who received a different agent, patients who had experienced a prior response to first-line gc and who were re-challenged with second-line gc had a better median ttp (11.0 months vs. 6.0 months, p = 0.02) and survived longer (4.0 months vs. 1.0 months, p = 0.02). No differences in os between non-gc regimens were evident. Conclusions: In patients with metastatic uc, overall outcomes remain poor, but compared with patients receiving other agents, the subgroup of patients re-challenged with second-line gc demonstrated improved ttp. Conventional chemotherapy regimens provide only modest benefits in the second-line setting and have largely been replaced with immunotherapy.

Expression and induction of three family 4 cytochrome P450 (CYP4)* genes identified from insecticide-resistant and susceptible western corn rootworms, Diabrotica virgifera virgifera.

We have previously determined that cytochrome P450-based oxidation is involved in resistance to the insecticides methyl parathion and carbaryl in geographically distinct Nebraska western corn rootworm populations. Three new family 4 cytochrome P450 (CYP4) gene fragments (CYP4AJ1, CYP4G18 and CYP4AK1) were cloned and sequenced from insecticide-resistant and -susceptible western corn rootworms. Insecticide bioassays indicated the resistant population employed in this study was significantly resistant to the insecticides methyl parathion and carbaryl. CYP4AJ1 and CYP4G18 were cloned from both genomic PCR and RT-PCR products, although only CYP4AJ1 contains an intronic region. Alignments of inferred amino acid sequences with other homologous insect CYP4 genes indicates a high degree of similarity. Northern analysis concurrently employing mixed probes representing each of the three rootworm CYP4 fragments identified increased mRNA transcript signals (i) in resistant rootworms and (ii) following induction by the P450 inducer pentamethyl benzene. These results support our previous documentation of P450-based insecticide resistance and suggest increased CYP4 transcript abundance can serve as a molecular resistance-associated marker.

Sequence analysis of hypothalamic parathyroid hormone messenger ribonucleic acid.

PTH-like peptides and messenger RNA (mRNA) have recently been detected in neural tissues, but it is uncertain whether this reflects the transcription of the PTH gene or that of a closely related gene. This possibility has, therefore, been investigated. PTH-like complementary DNA (cDNA) moieties of predicted size were readily generated from reverse transcribed brain (hypothalamic and extrahypothalamic tissue) and pituitary RNA, using polymerase chain reaction (PCR) with three sets of overlapping oligonucleotide primers designed to amplify PTH cDNA fragments of 285, 372, and 459 base pairs (bp). PCR reamplification of the largest hypothalamic moiety with an internal set of primers also generated a cDNA fragment of the predicted size (372 bp). Restriction endonuclease digestion with BstNI cleaved the largest hypothalamic cDNA moieties into smaller fragments of 217 and 242 bp, identical to the cleavage of parathyroidal PTH cDNA. Rapid amplification of cDNA ends of the 3'-flanking cDNA sequences also produced hypothalamic and extra-hypothalamic cDNA moieties identical in size (499 bp) to parathyroidal PTH cDNA. Southern analysis of these PCR and rapid amplification of cDNA end cDNA fragments further indicated homology with PTH cDNA. This homology was subsequently confirmed by nucleotide sequencing, which demonstrated complete homology between the neural and parathyroidal cDNA fragments. This homology extended over 673 bp (spanning nucleotides 31-709 of PTH cDNA), encompassing 95% of the entire parathyroidal PTH cDNA. The mRNA for this gene, determined by Northern blotting with a riboprobe for PTH mRNA, was of identical size to the parathyroidal PTH, but its abundance in brain was less than 0.01% of that expressed in the parathyroid glands. This transcript was not, however, detected in liver. The translation of this moiety in hypothalamic tissues was indicated by the presence of a protein in the rat hypothalamus that was immunoreactive with PTH-(1-84) antiserum and of comparable size to that in parathyroidal tissue. The abundance of this protein in hypothalamic tissue was approximately 0.25% of that in the parathyroid glands, suggesting tissue-specific differences in its rate of synthesis, processing, or degradation. These results, therefore, demonstrate that the brain is an extraparathyroidal site of PTH gene expression and suggest autocrine or paracrine roles for PTH in neural function.

Neonatal meningitis at Bustamante Hospital for Children: a retrospective study - abstract

Records of 36 neonates with meningitis were reviewed over a five-year period, between 1982 and 1986. The rate of neonatal meningitis was 18.5/1,000 neonatal admissions with a male predilection. Predisposing factors were identified in 30 per cent of neonates; late onset disease was the predominant type. Group B haemolytic streptococcus was the leading cause, followed by gram-negative bacteria. The long-term morbidity was 28 per cent; complications varied from mild, early onset seizures to permanent disability such as cerebral palsy. Seventy per cent of the complications arose in late onset disease type; gram-negative bacteria (60 per cent) were the predominant cause. The fatality rate was 3/36 (8 per cent) (AU)

Herpes simplex virus infections in immunocompromised Jamaican patients

Data are presented on 13 immunocompromised patients with herpes simplex virus (HSV) infection. Eleven patients had recurrent HSV infection. Eight had genital herpes, 3 had disseminated infection and two had localised extragenital infection. Nine patients had confirmed recurrent HSV-type 2 infection. The benefits of recent antiherpetic therapy in the prevention of recurrent HSV infections in immunocompromised Jamaican patients are discussed (AU)

Fever in children: ideas and illusions - abstract

Fever is a common symptom in children. Yet concepts vary between physicians and parents. We interviewed 120 mothers at three participating locations (University Hospital of the West Indies, Bustamante Hospital for Children and Shortwood Medical Centre) to ascertain their concepts and practices concerning fever in their children. None of the mothers used thermometers to detect fever; the majority (85 percent) were unable to define fever in terms of temperature. Tepid sponging with alcohol and administration of antipyretics were the measures most frequently undertaken to reduce fever. There is a need to educate parents and health-care personnel about fever and its management in children, particularly to discourage the use of topical alcohol (AU)

Genital herpes in Jamaica: a clinical and pathological study (1982-1984)

Five hundred and four patients with suspected genital herpes simplex virus (HSV) infection were investigated in Jamaica between 1982 and 1984. Of these, 100 (19.8 percent) were virologically confirmed. There were 12 patients with primary/first episode, 45 recurrent and 6 "provoked' type of genital herpes simplex virus infections. Genital herpes in women was more severe than in men. Eighty-eight per cent of genital herpes was confirmed by virus isolation. Forty HSV isolates were identified as HSV type 2. There was a sero-response in 75 percent primary, 18 percent recurrent and 17 percent provoked type of genital herpes. Virus isolation is the most sensitive and specific test for the diagnosis of genital herpes simplex virus infection. The measurement of serum anti herpes simplex complement-fixing antibodies was not useful in the diagnosis of suspected patients with genital ulcers and their contacts. The infectiousness of the virus, clinical manifestations, complications such as neonatal herpes infections, psychosocial problems and methods of prevention are issues that clinicians should discuss with patients with genital herpes (AU)

Risk factors for carcinoma of the uterine cervix in Jamaican women

Risk factors of cervical cancer include early age at coitus, multiple sexual partners and antibodies to herpes simplex virus, type 2 (HSV-2). To examine the interrelationships of these risk factors, a comparison was made between 78 histologically confirmed cancer cases (stages O-IV) and 151 control women in Jamaica. The rank of order of the percentages of control women with low socioeconomic status, first coitus before 20 years of age, first pregnancy before 20 years of age and more than two sexual partners were: 77, 97, 65, and 76 respectively. The percentage of women with cancer who had first coitus before 20 years of age (77) and 2 or more partners (55) were lower than that of controls. A third factor associated with cervical cancer is the presence of HSV-2 antibodies. The age-specific prevalence of HSV-2 antibodies varied from 7 percent to 32 percent in women aged 21-69 years. An increase in prevalence of HSV-2 was observed with increasing age. The age-adjusted prevalence was 11 per cent. The age-specific occurrence of HSV-2 antibodies in cancer cases were not statistically significant as compared with matched controls (p> 0.01). The data suggest that infection with HSV-2 is a covariable of venereal factors, and the role of the virus in the genesis of some cases of cervical cancer in Jamaican women may not be excluded (AU)