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Biomedical subjects

F Holmes

Publications and source records attributed to F Holmes.

32 records · Page 2Linked to original sources
PubMed1990

Relationship of age to histologic grade in prostate cancer.

We studied 4,968 cases of prostatic carcinoma to determine if there is a relationship between tumor grade and patient age at diagnosis. Cases were stratified into arbitrary age groups and classified as either better differentiated (Grades I and II) or worse differentiated (Grades III and IV). The 4,596 graded cases were distributed by stage as follows: Local 3,451 (75%), Regional 509 (11%), and Distant 636 (14%). When patients in all stages were considered together, the percentage of men with better differentiated tumors dropped from 77.8% of patients under 60 to 67.5% of patients 80 or older (P less than 0.00001). This trend for older patients to have more poorly differentiated tumors was also seen in patients with localized disease (P less than 0.0005). The fact that occult, biologically inactive prostate cancer is common in older men has led some to extrapolate that clinically apparent disease follows a more benign course in the elderly. Our findings suggest that, on the contrary, elderly men with clinically apparent disease have worse differentiated tumors than their younger counterparts.

Age Factors↗
PubMed1990

Survival in acute leukemia in elderly patients. No improvement in the 1980s.

Acute leukemia is more common in older people than in the young or middle-aged. However, the possibilities of achieving remission or prolonging survival are both inversely correlated with increasing age. We studied survival in 118 acute leukemia patients over the age of 64 seen at a university hospital from 1970 to 1987. Seventy percent had myeloid morphology. Median survival times were 106 days in those diagnosed in the 1970s and 71 days for those diagnosed in the 1980s. This was little changed from an earlier series from the same hospital extending back to the 1940s in which median survival was 69 days. Considering the two decades separately, age at diagnosis, sex, race, type of leukemia, and whether or not disease-specific treatment was applied had no significant effect on survival duration. Acute leukemia in the older patient demands difficult medical and ethical choices. Supportive therapy provides immediate comfort and relatively limited morbidity with certainty of death within a few months. Disease-specific therapy causes immediate morbidity for all, shortened life for the majority, and extended life for the minority.

Acute Disease↗
PubMed1990

A phase II study of mitoxantrone, etoposide, and thiotepa with autologous marrow support for patients with relapsed breast cancer.

To further improve the effect of high-dose chemotherapy in the treatment of locally advanced and metastatic breast cancer, we sought to develop a second active high-dose noncross-resistant regimen to use in tandem with our customary high-dose regimen of cyclophosphamide, etoposide, and cisplatin (CVP). We performed a phase II trial of high-dose mitoxantrone 30 mg/m2, etoposide 200 mg/m2 every 12 hours x 6, and thiotepa 250 mg/m2 x 3 days (MVT) in 31 patients with heavily pretreated metastatic breast cancer and one with locally advanced chemotherapy-refractory breast cancer. These patients were ineligible for high-dose CVP chemotherapy because of the amount of prior treatment and poor-response status. Of the 32 patients, 14 responded to cycle 1, did not experience any grade 4 toxicity, and received a second cycle of MVT. Overall, seven of 31 patients achieved a complete response (CR; 23%). Four of the 14, who were partial responders to the first cycle, achieved a CR after the second cycle. The overall response rate was 19 of 31 (61%) with an overall median freedom from progression of 4 to 5 months and an overall median survival of 9 months. Toxicity consisted primarily of mucositis (grade 3 or 4 in 69%). The results indicate that high-dose MVT produces significant activity, even in heavily pretreated patients. Administration of a second cycle of high-dose therapy with MVT increased the CR rate, and the morbidity and mortality from the second cycle were not greater than that for the first cycle. Because of the high incidence of grade 3 or 4 mucositis with this regimen, we are currently completing a follow-up study of high-dose mitoxantrone and thiotepa alone.

Adolescent↗
PubMed1990

Treatment of estrogen receptor-negative or hormonally refractory breast cancer with double high-dose chemotherapy intensification and bone marrow support.

We have used high-dose therapy followed by randomization to receive or not receive autologous bone marrow infusion in 58 stage IV breast cancer patients (all were estrogen receptor-negative [ER-] or primary hormonal refractory). Patients received a median of four courses of induction chemotherapy and if stable or responding received two courses of intensive therapy with cyclophosphamide 4.5 to 5.25 g/m2, etoposide 750 to 1,200 mg/m2, and cisplatin 120 to 180 mg/m2 (CVP). The complete remission (CR) rate after completion of the induction and intensive phases was 55%. Median progression-free interval from induction is 57 weeks with a projected 2-year progression-free survival of approximately 25%. Six of seven patients followed for greater than 2 years are still progression-free. Three favorable features predicted for improved progression-free survival are the following: (1) absent liver involvement, (2) absent soft tissue involvement, and (3) less than or equal to two disease sites (P values of .001, .013, and .048, respectively). Hormonal and menopausal status did not predict for progression-free survival. Major toxicities were infectious secondary to neutropenia, with a 93% incidence of fever and a 38% incidence of sepsis. The treatment-related mortality rate was 9%, with three infectious, one coronary, and one late hemorrhage-related death of unknown cause. Longer follow-up is still needed to truly evaluate the possibility of long-term disease-free survival, but further studies of this approach to high-dose intensification in poor prognostic groups of stage IV breast cancer appear warranted.

Adult↗
PubMed1989

Oral ciprofloxacin therapy for infections in cancer patients.

Forty six episodes of infection in 43 cancer patients were treated with oral ciprofloxacin at a dose of 750 mg every 8 h. The overall clinical response was 85%. Patients with microbiologically proven infections had a higher response rate (90%) than patients with infections from whom no causative organism(s) could be isolated (69%). Two of three neutropenic patients responded favourably. Favourable responses were seen in a variety of infections including bacteraemia, urinary tract infection, respiratory tract infection and skin and soft-tissue infection. Resistance to ciprofloxacin developed in one isolate of Pseudomonas aeruginosa. Side effects were mild and were predominantly gastrointestinal in nature. Orally administered ciprofloxacin is safe and effective for the therapy of many serious infections in cancer patients. However, more data are required in patients who are neutropenic.

Adult↗
PubMed1988

Anal cancer in women.

We studied predisposing factors in 56 women with anal cancer, comparing them with 56 matched controls drawn from the population. A detailed pretested questionnaire was administered to each study subject in a structured interview and blood was drawn for detection of herpes simplex virus antibodies by radioimmunoassay. Pathologic material from cases was obtained and evidence of human papilloma virus infection was sought. By univariate analyses we found associations between anal cancer and positive herpes simplex virus 2 titer (p = 0.0017), cigarette smoking (p = 0.0028), previous positive or questionable cervical Papanicolaou smear (p = 0.0124), and increasing number of sexual partners (p = 0.0224). By the multivariate technique of logistic regression there were independent and significant associations with cigarette smoking (p = 0.0126), previous use of hemorrhoid preparations (p = 0.0149), and history of disturbed bowel habits for greater than 1 mo (p = 0.0273). Anal cancer in women is a rare disease associated with cigarette smoking and sexual experience. Its association with previous anorectal disease is unclear and deserving of further study.

Adult↗
PubMed1988

Phase II evaluation of Ly156758 in metastatic breast cancer.

Fourteen patients with disseminated breast cancer with primary or secondary resistance to tamoxifen were treated with LY156758. There were no complete or partial responses and 1 patient showed a minor response. These data illustrate that LY156758 did not have significant antitumor activity in patients previously treated with tamoxifen therapy.

Breast Neoplasms↗
PubMed1985

Evaluation of mitoxantrone cardiac toxicity by nuclear angiography and endomyocardial biopsy: an update.

Sixty-six patients who underwent endomyocardial biopsy for detection of mitoxantrone (Novantrone; dihydroxyanthracenedione) cardiac toxicity were evaluated. All but one had breast cancer, 29 had received prior doxorubicin and 29 of the 37 patients who had not had prior doxorubicin received it or another anthracycline subsequently. Endomyocardial biopsy was carried out initially after four courses of chemotherapy with increasing intervals thereafter. Although cardiac ejection fraction was determined before each course of chemotherapy, our data are limited to cardiac ejection fractions from our own institution which were repeated approximately every four courses. Endomyocardial biopsy changes consisting of dilatation of the sarcoplasmic reticulum with vacuole formation, and myofibrillar dropout are similar to the early changes of anthracycline cardiomyopathy. While there was a slight suggestion of increasing biopsy grade with increasing mitoxantrone dose, no significant changes in cardiac ejection fraction could be associated, regardless of prior doxorubicin therapy. We concluded that mitoxantrone does show morphologic evidence of cardiac toxicity; however, the structural changes are minor and are haemodynamically insignificant. Determination of how much mitoxantrone treatment may contribute to the deterioration of pre-existing doxorubicin damage must await the outcome of longer follow-up.

Adult↗
PubMed1981

Simultaneous Streptococcus and picornavirus infection. Muscle involvement in acute rhabdomyolysis.

Streptococci seldom invade muscle in healthy people with intact integument. However, infection with another agent simultaneously may change this general observation. In a two-week period we encountered dual infections with group A, beta-hemolytic streptococci and a picornavirus in each of two hospitalized patients. Both were acutely ill; one died. Renal failure developed in the patient who survived and rhabdomyolysis was demonstrated in the patient who died. Picornavirus titer increases were demonstrated in the patient who survived, and viral inclusions in muscle cells were demonstrated by light microscopy in necropsy specimens and confirmed by electron microscopy in the second patient. We believe that streptococcal invasion of muscle may be facilitated during an outbreak of certain picornavirus infections.

Acute Disease↗
PubMedDate not supplied

Subarachnoid spinal analgesia. A comparative survey of current practice in Scotland and Sweden.

A postal inquiry into the current use of subarachnoid spinal analgesia obtained replies from approximately 70% of consultants in both Scotland and Sweden. Although medico-legal anxiety was still an important feature of Scottish practice, the publication of large series with a low incidence of complications had also exerted some influence, and 40% of consultants employed the technique. In contrast, 70% of Swedish replies indicated current use of spinal analgesia and the individual frequency of administration was considerably higher. The present popularity of epidural analgesia has contributed to some decline in the use of subarachnoid spinal analgesia in Sweden, particularly in the case of longer surgical procedures. Anaesthetists in both countries expressed dissatisfaction with the limited choice of available spinal agents and considered their duration of action to be inadequate. In Scotland, conditional indications, such as diabetes mellitus and respiratory disease, were of major importance, whereas Swedish users more often specified surgical procedures for which subarachnoid spinal analgesia was considered to be the anaesthetic of choice. Few anaesthetists had experience of complications and no major neurological sequelae were reported. More than 80% of replies indicated that subarachnoid spinal anaesthesia had a useful place in anaesthetic practice.

Anesthesia, Spinal↗