PubMed HealthSearch

Biomedical subjects

J Kirkwood

Publications and source records attributed to J Kirkwood.

18 recordsLinked to original sources

Isolation of a new foamy retrovirus from orangutans.

We have isolated a new foamy virus from blood samples taken from two apparently healthy orangutans (Pongo pygmaeus). The older orangutan has since died with encephalopathy after a brief acute illness, while the younger one, his grandson, remains well. These animals and 12 other orangutans had specific antibodies to foamy virus as measured by immunofluorescence. The new foamy virus and the antisera showed strong and specific neutralization, with only weak cross-reaction with other simian foamy virus strains. Southern blotting with gag and env probes of human foamy virus and PCR amplification showed that the new foamy virus, designated SFV-11, is related to, yet distinct from, previously characterized strains from humans, chimpanzees, and monkeys.

Animals

Sequence analysis of the PrP protein from two species of antelope susceptible to transmissible spongiform encephalopathy.

The sequence of the coding regions of the PrP genes of the Arabian oryx and greater kudu have been determined and compared with the related sheep and bovine PrP gene sequences. The oryx gene sequence was found to be very closely related to that of the sheep, encoding just one amino acid difference. The greater kudu gene sequence was found to be more closely related to the bovine, encoding four amino acid differences. The possible influence that the gene sequences have on the transmission of spongiform encephalopathy to these antelope species is discussed.

Animals

Mastectomy versus breast conservation surgery: mental health effects at long-term follow-up.

Between 1984 and 1989, 129 Stage 1 and Stage 2 breast cancer patients were entered into a behavioral study in Pittsburgh. Approximately 70% of these patients had elected to have breast conservation (lumpectomy) surgery, with the remainder choosing mastectomy. Using the Profile of Mood States, a measure of perceived social support, and Karnofsky ratings of physical functional status, patients were assessed 3 to 5 days following surgery and again 3 and 15 months following surgery. The data were analyzed using a repeated-measures analysis of covariance, adjusting for aggressiveness of chemotherapy. Compared to mastectomy patients, patients who received breast conservation surgery were rated as more functional by observers, but they perceived themselves as having less energy and less emotional support, especially over the first 3 months of the recovery period. Because there is accumulating evidence that emotional support may act as a stress buffer in various populations and may have survival value, these findings may be particularly troublesome. This study shows that breast conservation surgery is not a psychosocial panacea. Patients whose breasts are spared, especially younger patients, have psychological symptoms that appear acutely worse in the short run and, in the end, are similar to those of patients who elect to have mastectomies. Therefore, patients choosing lumpectomies are not necessarily psychosocially better off than those electing to have mastectomies. Additionally, these patients, particularly younger patients, may require greater social support and potential mental health interventions than they seem to be receiving.

Adaptation, Psychological

Phase II trial of fluorouracil and recombinant interferon alfa-2a in patients with advanced colorectal carcinoma: an Eastern Cooperative Oncology Group study.

In a pilot clinical trial, treatment of patients with advanced colorectal carcinoma with the combination of fluorouracil (5FU) and recombinant interferon alfa-2a (IFN) resulted in objective tumor regression in 62% of patients. To confirm these findings in a multiinstitutional setting, a phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG) in 1989. The treatment regimen was identical to that used in the earlier study: 5FU 750 mg/m2/d for 5 days as a continuous infusion followed by weekly outpatient bolus therapy and IFN 9MU subcutaneously beginning day 1 and administered three times per week. Doses were modified for gastrointestinal, hematologic, and neurologic toxicity and for fatigue, similarly to those used in the previous pilot trial. Thirty-eight patients were registered; 36 are evaluable for response (one lost to follow-up and one with nonmeasurable disease). All patients had metastatic or locally recurrent disease beyond the scope of resection; 31 of 38 had liver metastases, and 20 of 38 had two or more sites of involvement. Eight patients had grade 4 toxicities, including sepsis (nonneutropenic) (one), watery diarrhea (two), and granulocytopenia (six). Grade 3 neurologic toxicities were observed in two (5%) patients and included slurred speech and gait disturbance. Objective response was 42% (95% confidence interval [Cl], 27% to 58%), including one clinical complete responder and 14 partial responders. Among the responding patients, the median time to treatment failure was 8 months. Two patients remain on treatment at 10+ and 16+ months: median survival has not been reached. The results of this multiinstitutional trial suggest that the addition of IFN to 5FU enhances the objective response rates achieved in patients with advanced colorectal carcinoma and that the toxicities of this regimen are acceptable.

Adult

Estrogen receptor concentration and social factors as predictors of natural killer cell activity in early-stage breast cancer patients. Confirmation of a model.

Previous work of ours has demonstrated that a significant amount of natural killer (NK) activity variance after surgery in stage I and II breast cancer patients could be accounted for by both the estrogen receptor (ER) status of the tumor and by social factors, namely, perceived social support and seeking social support as a general coping strategy. As considerable evidence has accumulated that social support in both animal and human populations may have survival value, we sought to test the reliability of this regression model, using coping and perceived support factor values obtained at 3 months after surgery to account for concurrent follow-up NK activity in this serially assessed group of patients. It was found that the most significant variable predicting NK activity at follow-up was tumor ER concentration, with higher NK activity associated with ER- status. In addition, seeking social support as a coping strategy, as well as the perceived quality of support, also entered the model to account for a significant amount of NK activity variance (multivariate F = 5.25, p less than 0.001). If, as the literature suggests, NK activity is relevant to breast cancer control, and since ER- tumors have a worse prognosis, we suggest here that perhaps such tumors are resistant to control by NK cells because they lack the ability to attract an accumulation of effector cells to the tumor site, or because blocking factors at the site of the tumor prevent local tumor control at the site of action. The finding related to social support also replicates results from an independent sample of breast cancer patients. This finding, taken together with other evidence that this social variable is associated with longer survival in breast cancer populations, underscores the potential importance of this social support variable. Our findings also suggest one possible immunological variable involved, with potential clinical significance, for this patient population.

Adult

Dermatitis produced by applications of monobenzone in patients with active vitiligo.

Six patients with spreading vitiligo treated with applications of monobenzone developed a vesicular dermatitis. The eruption was restricted exclusively to the pigmented areas of the skin. Patch tests applied to pigmented and depigmented skin produced an inflammatory response only within the pigmented areas. The explanation for this puzzling phenomenon is not known.

Adult

Demographic study of clinically atypical (dysplastic) nevi in patients with melanoma and comparison subjects.

We examined 296 patients with a history of melanoma and 145 controls for the presence of atypical (dysplastic) nevi. We found that 34% of patients with melanoma and 7% of controls had clinically atypical (dysplastic) nevi. Patients and controls with atypical (dysplastic) nevi had more nevi than the subjects without. The number of nevi varies negatively and significantly with age (r = 0.37, P less than 0.001). Ten % of patients and controls had hypopigmented halos around one or more nevi. Both patients and comparison subjects with atypical (dysplastic) nevi tended to have this subtle variant of halo nevi more often than those without (r = 0.17, P less than 0.01). The number of nevi on the irides of melanoma patients was greater than that in the comparison group. The results of this study suggest that patients with a melanoma exhibit more commonly cutaneous and ocular pigmentary lesions than comparison subjects without a melanoma.

Adolescent

Uveal findings in patients with cutaneous melanoma.

A study Of the uveas of white patients with known cutaneous melanoma and white control subjects showed that patients with cutaneous melanoma had a significantly higher frequency of iris nevi (101 of 197 patients, 51%) than control subjects (58 of 147 subjects, 39%). The frequency of choroidal nevi was also higher in the group with cutaneous melanoma but the number (eight of 197 patients compared with two of 147 control subjects) involved was too small for statistical significance to be assessed. Patients with cutaneous melanoma, particularly women, had more skin nevi than did control subjects.

Choroid Neoplasms

New observations on vitiligo and ocular disease.

We examined 223 consecutive patients with vitiligo for ocular disease and 154 consecutive patients with uveitis for vitiligo to better determine the nature of the relationship between vitiligo and ocular disease. Of the 129 patients whose uveitis had an unknown cause, seven (5.4%) had cutaneous depigmentation, poliosis, or early graying of hair. The incidence is 0.5% in the general population (P less than .02). None of the 25 patients whose uveitis had a known cause had vitiligo. Eleven (4.8%) of 223 patients with vitiligo had uveitis at the time of the study or had had it within the previous two years. Of 27 patients in whom vitiligo was associated with cutaneous melanoma, five (18.5%) had had uveitis within the previous two years. In three of these five, the uveitis began within one month of the appearance of cutaneous changes. Evidence of old chorioretinal scars were present in 69 of 223 patients with vitiligo (30.9%) but in only two of 148 control patients (P less than .001). Sixty of 223 patients with vitiligo (26.9%) had evidence of hypopigmentation or atrophy of the retinal pigment epithelium, or both, not related to old chorioretinitis or macular degeneration but only six of 148 controls did (P less than .001).

Adolescent

Improved survival for patients with advanced carcinoma of the head and neck treated with methotrexate-leucovorin prior to definitive radiotherapy or surgery.

Patients presenting with Stage III-IV squamous carcinoma of the head and neck often relapse following aggressive surgery and/or radiotherapy. In an attempt to increase survival in this high risk group of patients, HD-MTX, 3 gm./m2/dose, given weekly, was administered to 21 inoperable patients with Stage III/IV squamous carcinoma of head and neck prior to, and for 1 month after, definitive surgery and/or radiotherapy. Six of 11 patients (55%) who showed a significant response (greater than 50% reduction in tumor volume) to HD-MTX are alive and free of tumor greater than 38 months following treatment (p = 0.6) (Fisher Exact Test). Responder median survival is greater than 38 months while non-responder median survival is 15 months (p = .02) (Log Rank Test). For the entire treatment group, at a mean duration of 44.2 months following initiation of therapy, 7 patients (33%) remain alive and free of tumor. Patients responding to induction MTX-LCV more often become eligible for combined modality approach than did the non-responder group. This "downstaging" of the tumor prior to aggressive surgery or radiotherapy may be responsible for the increased survival rate seen in those patients who responded to MTX-LCV.

Carcinoma, Squamous Cell

Clinical and biochemical assessment of a modified evaporated milk for infant feeding.

A clinical and biochemical evaluation has been made of a new milk formula, Modified Carnation milk (MCM), based on cows' milk but with the mineral content and concentration of caloric nutrients altered to make it correspond more closely to human milk. MCM produced higher plasma calcium and magnesium concentrations in 6-day-old infants than those produced by unmodified evaporated and dried milks, achieving concentrations closer to those of breast milk. Plasma free amino acid concentrations in MCM-fed infants are nearer breast-fed values than those in unmodified milk-fed infants where higher individual plasma amino acid concentrations persist during the first 3 months. MCM-fed infants had low plasma urea concentrations and lower urine osmolalities at 6 days, 3 weeks, 6 weeks, 3 months, and 6 months than infants fed on the evaporated and dried milks, and similar plasma urea and urine osmolalities to those of breast-fed infants. MCM is likely to be superior to unmodified evaporated and dried milks in preventing convulsions of the hypocalcaemic/hypomagnesaemic/hyperphosphataemic type, and seems less likely to cause hypertonic dehydration. MCM is easily prepared, readily accepted by babies, and appears to be nutritionally adequate for the feeding of term infants.

Amino Acids

Pharmacology of some oral penicillins in the newborn infant.

Serum and urine concentrations of ampicillin, amoxycillin, and flucloxacillin achieved after oral administration have been measured in 27 newborn infants. Compared with adults and children, newborn infants show a delay in achieving adequate blood concentrations, presumably due to delayed absorption. However most infants achieve therapeutic concentrations in the serum. Infected newborn infants should be given these antibiotics by intramuscular injection for the first dose, but thereafter oral therapy (25 mg/lg every 6 hours begun concomitantly) should be satisfactory. The better absorption of amoxycillin compared with ampicillin reported in adults has not been confirmed in the newborn infant.

Administration, Oral

Perceived social support and tumor estrogen/progesterone receptor status as predictors of natural killer cell activity in breast cancer patients.

This report is concerned with the prediction of natural killer (NK) cell activity in 61 Stage I and II breast cancer patients, between the ages of 25 and 70, who were accrued to this project. All baseline interview and testing data were obtained either just before patients were discharged from the hospital, or at their first outpatient visit, within two weeks of discharge. A major interest of this project is the predictive value of perceived social support, as a potential "stress" buffer, related to NK activity. In the main model reported here, we found that a significant amount of NK activity variance could be explained by five variables. Higher NK activity could be predicted by the perception of high quality emotional support from a spouse or intimate other, perceived social support from the patient's physician, estrogen receptor-negative tumor status, having an excisional biopsy as surgical treatment, and actively seeking social support as a major coping strategy (R2 = 0.33, F(5,55) = 5.5, p less than 0.0004). Findings are discussed in terms of host interaction with tumor endocrine status, and the role that social support might play in modulating such activity.

Adult