Long-term follow-up of radiotherapy for prostate cancer.

PURPOSE: To determine the long-term outcome of radiotherapy for prostate cancer. METHODS AND MATERIALS: A total of 136 consecutive patients with prostate cancer underwent primary radiotherapy. All but 4 patients received 6000 cGy to the prostate. The minimal follow-up was 22.9 years. RESULTS: Of the 136 patients, 93 had Stage B (T2), 9 Stage A (T1), and 34 Stage C (T3). Sixty-nine percent of the patients developed recurrence, and 51% of all patients died of prostate cancer. The recurrences developed at a steady state throughout the length of follow-up. One half the recurrences occurred after 10 years, and recurrence was still observed >20 years after treatment. The survival rate at 5, 10, 15, 20, and 25 years was 81%, 59%, 37%, 16%, and 10%, respectively. The recurrence-free survival rate at 25 years was 17%. The median survival for Grade 3-4 patients was 6.3 years and for Grade 1-2 patients was 13.0 years. The median survival for those with T1 tumors was 12.9 years; T2 tumors, 12.4 years; and T3 tumors, 9.5 years. CONCLUSION: Despite favorable early results, with long-term follow-up, patients continued to experience prostate cancer recurrence. Unless they died an intercurrent death, they were highly likely to develop recurrence and die of prostate cancer. The conclusions from treatment studies with <15 years of follow-up should be viewed as preliminary.

A cloned gene of Cryptosporidium parvum encodes neutralization-sensitive epitopes.

Two mAb, C6B6 and 7D10, each significantly reduced infection of mice by Cryptosporidium parvum and reacted with a 23-kDa glycoprotein (p23) of geographically disperse C. parvum isolates. The antibodies were used to identify plaques in a cDNA library prepared from C. parvum sporozoite mRNA. cDNA insert sequences from positive plaques were determined and used to isolate additional clones encoding p23 coding sequences. A consensus open reading frame of 333 base pairs, encoding 111 amino acids, was identified in this collection of cDNAs. The predicted amino acid sequence contained one N-glycosylation site, but lacked hydrophobic membrane spanning regions. Epitope mapping revealed that mAb 7D10 defines the linear epitope QDKPAD which occurs twice in the C terminal region of the peptide encoded by the ORF. This same C terminal peptide region contains a non-linear epitope bound by mAb C6B6. Serum from mice immunized with synthetic C terminal peptide reacted with sporozoite p23. The occurrence of neutralization-sensitive epitopes encoded by defined regions of the C. parvum genome suggests that recombinant proteins or synthetic peptides containing these epitopes may prove useful for inducing immune responses that diminish infection.

Usefulness of positive troponin-T and negative creatine kinase levels in identifying high-risk patients with unstable angina pectoris.

Troponin-T was measured in patients with chest pain and negative creatine phosphokinase-MB isoenzymes. Patients with elevated troponin-T had a significantly greater risk of cardiac events over the next 6 months than patients with normal troponin-T.

Serum prostate-specific antigen levels in stage A1 prostatic cancer.

Quantitation of serum prostate-specific antigen (PSA) has recently come into widespread use. Controversy exists regarding its usage in screening for carcinoma of the prostate (CAP), based partly on concern that it may detect small foci of CAP that will not cause any significant morbidity or mortality. This study was conducted to evaluate serum PSA levels in stage A1 CAP. The authors identified 143 consecutive men who had PSA levels drawn within 8 weeks of transurethral resection performed for presumed benign prostatic hyperplasia. One hundred twenty-four of these (86.7%) had no cancer, 11 (7.7%) were found to have stage A1 CAP, and eight (5.6%) were found to have CAP beyond stage A1. The mean PSA level in patients with stage A1 CAP was 2.3 ng/mL, and the benign (no cancer) group had a mean PSA level of 3.8 ng/mL. Ten of the 11 patients in the stage A1 group had PSA values less than 4.0 ng/mL. Therefore, it was found that most patients with stage A1 CAP did not have elevated PSA levels. In the authors' experience, elevation of PSA levels caused by CAP is indicative of a tumor burden greater than that found in stage A1 CAP.

Hormone withdrawal symptoms in oral contraceptive users.

OBJECTIVE: To measure the timing, frequency, and severity of hormone-related symptoms in oral contraceptive (OC) users, specifically to compare active-pill with hormone-free intervals. METHODS: Using daily diaries, women recorded pelvic pain, bleeding, headaches, analgesic use, nausea or vomiting, bloating or swelling, and breast tenderness during active-pill intervals and hormone-free intervals. Participants either had no prior OC use, had taken OCs and were restarting, or had been taking OCs continuously for 12 months or longer. RESULTS: Two hundred sixty-two women, 26 with no previous OC use, 43 prior users, and 193 current users, provided daily records of hormone-related symptoms. Subjects with no prior OC use and prior users restarting were similar in no recent OC use, and because of the small sample, they were pooled for analysis as new-start OC users. Current users had patterns of symptoms that were more frequent during hormone-free intervals than during the three active-pill weeks. These included pelvic pain (70% versus 21%, P < .001), headaches (70% versus 53%, P < .001), use of pain medication (69% versus 43%, P < .001), bloating or swelling (58% versus 19%, P < .001), and breast tenderness (38% versus 16%, P < .001). Similar patterns were seen in new-start OC users after the first cycle. Among new-start OC users, menstrual flow patterns, headache, bloating or swelling, and breast-tenderness symptoms decreased during the three cycles to approach those levels of current users. CONCLUSION: Almost all symptoms assessed were significantly worse during the 7-day hormone-free interval than during the 21 days of hormone-containing pills.

Evaluation of age-specific normal ranges for prostate-specific antigen.

OBJECTIVES: To compare the traditional normal range (TNR) of 0.0 to 4.0 ng/mL for serum prostate-specific antigen (PSA) to age-specific normal ranges (ASNRs). METHODS: An autopsy series of completely sectioned, clinically benign prostates from 171 consecutive Caucasian men over the age of 40 years was selected. These patients were divided into those having no prostate cancer at autopsy, prostate cancer less than 1 cc in volume, and prostate cancer at least 1 cc in volume. The PSA values of each group were compared using both the TNR and the ASNR. RESULTS: Twenty-three of 105 (21.9%) patients with no cancer had elevated PSA values by the TNR, whereas only 18 (17.1%) were elevated using the ASNR. Nine of 54 (16.7%) with cancer less than 1 cc were elevated using the TNR, and 7 of 54 (13.0%) using the ASNR. Of 12 patients with cancer at least 1 cc, all had elevated PSA levels using the TNR and 11 (91.7%) were elevated using the ASNR. All discrepancies between the TNR and ASNR occurred in the 60- to 79-year age range. CONCLUSIONS: Use of ASNRs appears helpful in increasing the specificity of PSA by eliminating some elevated values in patients in their 60s and 70s.

Randomized, multicenter comparison of oral granisetron and oral ondansetron for emetogenic chemotherapy.

STUDY OBJECTIVES: To compare the antiemetic effectiveness and safety of oral granisetron plus dexamethasone with those of oral ondansetron plus dexamethasone administered before emetogenic chemotherapy. DESIGN: Randomized, prospective, multicenter, open-label study. SETTINGS: University-teaching hospital and veterans health care system. PATIENTS: Sixty-one chemotherapy-naïve patients scheduled to receive emetogenic antineoplastic agents. INTERVENTION: A single-dose oral granisetron 1 mg and dexamethasone 12 mg or single-dose oral ondansetron 16 mg and dexamethasone 12 mg was administered before chemotherapy. MEASUREMENTS AND RESULTS: Twenty-four hours after administration patients were contacted to assess nausea, emesis, and adverse events. There were no statistical differences in frequency of nausea or emesis between groups. Seventy-six percent and 82% of patients receiving ondansetron and granisetron, respectively, experienced no emesis 24 hours after chemotherapy. Complete protection from nausea occurred in 58% and 46% of patients receiving the drugs, respectively. Adverse events were similar between groups. CONCLUSION: Oral granisetron 1 mg and ondansetron 16 mg plus dexamethasone are safe and effective in preventing nausea and vomiting related to emetogenic chemotherapy.

A prospective evaluation of risk factors for infections from dog-bite wounds.

OBJECTIVE: To define risk factors for infections from dog- bite wounds and to model the probability of wound infection in patients presenting without infection who are treated as outpatients. METHODS: A prospective survey of 769 consecutive dog-bite victims presenting over a two-year period to a community hospital emergency department (ED) with an emergency medicine residency program. A standardized wound-cleaning protocol was used, which included debridement and wound closure when indicated. Wounds were examined for infection at follow-up. Variables analyzed included demographic data (patient age, gender, race); wound information (wound age, type, number, location, depth); and treatment (prior to hospital, ED debridement, suturing, tetanus or rabies shots, antibiotics). RESULTS: There were 734 patients with complete records. These patients had a mean age of 13.4 +/- 13.2 years (range, 4 months to 71 years). Infection was evident in 2.5% of the wounds upon presentation. There were 704 patients (765 wounds) managed as outpatients and without wound infection upon presentation. Wounds were distributed as follows: 26.7% head/neck, 20.4% hand, 15.7% arm, 10.1% trunk, 9.5% thigh, 15.9% leg, and 1.7% foot. There were 32.9% puncture, 39.9% full-thickness, and 60.1% partial-thickness wounds. Wound infections were diagnosed in 2.1% Of these wounds at follow-up. Wounds requiring surgical debridement had a sevenfold higher infection rate (p = 0.01). Patients more than 50 years of age had a sixfold higher infection rate than younger patients (p = 0.05). Stepwise logistic regression found the following variables to be the best predictors for wound infection: full-thickness [p = 0.006, odds ratio (OR) = 6.23], female gender (p = 0.048, OR = 2.88), and wound debridement (p = 0.024, OR = 5.01). Combinations of these three variables predict infection rates from 0.35% to 23.9%. CONCLUSION: A low wound infection rate was seen in this cohort of dog-bite victims who were treated on an outpatient basis. Wound depth, patient gender, and wound debridement were the clinical variables that best predicted the likelihood of developing infection. Future interventional studies should concentrate on wounds with high probabilities of infection.

Testosterone deficiency as a risk factor for hip fractures in men: a case-control study.

The objective of this study was to determine whether decreased gonadal function is a risk factor for hip fracture in elderly men. The study was a matched case-control study performed at an in-hospital orthopedic service at a semi-rural and academic tertiary care center. The patients were seventeen men who presented with hip fractures after simple falls over a 10-month period, 11 men with a history of hip fractures in the preceding 25 months, and 28 randomly selected age-, race-, and living status-matched control subjects (mean age 73 years). Serum pooled total testosterone (9.2 +/- 5.5 nmol/L vs. 12.8 +/- 5.4 nmol/L; p less than 0.02) and free testosterone (37.9 +/- 18.8 pmol/L vs. 48.4 +/- 20.6 pmol/L; p less than 0.03) were significantly lower in hip fracture vs. control patients. Testosterone deficiency was found in 20 (71%) hip fracture men vs. 9 (32%) of the controls (p = 0.003; odds ratio 5.3). Analysis of testosterone values within the stratum of absence of any chronic disorder revealed similar results. Serum 25-hydroxyvitamin D levels were significantly lower in the hip fracture group than in control men (p less than 0.001). The conclusion is that gonadal deficiency appears to be an important and heretofore understudied risk factor for hip fractures in men. Prevention of hip fractures in men may involve early recognition and treatment of testosterone deficiency.

Use of age-specific normal ranges for serum prostate-specific antigen.

BACKGROUND: The traditional normal range for prostate-specific antigen has been 0.0 to 4.0 ng/mL. Two different age-specific normal ranges have been proposed, one by Oesterling et al and the other generated by the Prostate Cancer Awareness Week experience. METHODS: We studied 213 consecutive cases of biopsy-proven prostate adenocarcinoma to evaluate age-specific normal ranges for prostate-specific antigen. We examined each patient's age, stage of disease, and serum concentration of prostate-specific antigen at the time of diagnosis. The three normal ranges were applied to each case. RESULTS: The patients ranged in age from 45 to 87 years. At all stages of disease, more patients had elevated serum prostate-specific antigen values using the traditional normal range as opposed to either age-specific normal range. These discrepancies were most obvious for stage II disease, in which 93 of 119 cases (78%) were elevated according to the traditional normal range versus 78 of 119 cases (66%) according to the Oesterling et al range and 80 of 119 cases (67%) according to the range defined during Prostate Cancer Awareness Week. For patients aged 40 to 59 years, all three normal ranges provided identical results (18 of 22 [82%] cancers detected). CONCLUSIONS: Use of either age-specific normal range would have missed more than 10% of stage II prostate adenocarcinomas in patients over the age of 60 years. This indicates that caution should be exercised when applying age-adjusted normal ranges for serum concentrations of prostate-specific antigen in patients of that age group.

Complete blood count indices in colorectal carcinoma.

Since carcinomas of the colon or rectum are associated with blood loss, we wondered if complete blood count data were suggestive of iron deficiency in cases of colorectal carcinoma. The mean corpuscular volume and especially the red blood cell distribution width are thought to be more sensitive to early iron deficiency than the hemoglobin value. These values were recorded from a series of 98 consecutive cases of colorectal carcinoma and compared with an age-matched control group consisting of patients with no history or clinical suspicion of malignant neoplasm. We found that the hemoglobin level, mean corpuscular volume, and red blood cell distribution width in patients with colorectal carcinoma do not generally show evidence of iron deficiency. The addition of the mean corpuscular volume and red blood cell distribution width to the hemoglobin value does not seem to increase the sensitivity of the complete blood count in the detection or clinical suspicion of colorectal carcinoma.

Neuroaxonal degeneration in sheep grazing Sorghum pastures.

During the fall of 1992, 250 (10%) of 2,500 Rambouilet cross feeder lambs grazing Sorghum bicolor developed neurologic signs including weakness, ataxia, head shaking, knuckling of the fetlocks, inability to rise, and opisthotonos. One hundred fifteen (46%) of the affected lambs died. Twenty of the surviving lambs exhibited residual neurologic signs of ataxia when stressed. At the same time, 275 (25%) of 1,100 ewes grazing a nearby sudex pasture (S. sudanese x S. bicolor) gave birth to lambs that were weak and unable to rise. Newborn lambs exhibited extensor rigidity and opisthotonos when assisted to a standing position. The dystocias that occurred were due to lambs with contracted limbs (arthrogryposis). All affected lambs died or were euthanized. Histologic examination of the brains of 3 feeder lambs and 9 newborn lambs revealed similar microscopic lesions. The predominant change was the presence of focal axonal enlargements (spheroids) in the proximal segments of axons, which were restricted to the nuclei of the medulla, cerebellum, and midbrain. In addition, the spinal cord contained spheroids in the ventral horn gray matter of the 6 newborns examined. Ultrastructurally, the spheroids were composed of aggregates of neurofilaments, mitochondria, vesicular bodies, and dense bodies bounded by a thin myelin sheath. There was mild gliosis in the more severely affected animals of both groups. There was minimal Wallerian degeneration in the white matter adjacent to affected nuclei in the brain and the ventromedial and dorsolateral funiculi of the spinal cord. This is the first detailed report of Sorghum toxicity in sheep.

Cranial teratomas in two domestic ducks (Anas platyrhynchos domesticus).

Teratomas are rare tumors in domestic fowl, and none have been reported in the cranial area of ducks. Clinical signs and gross and microscopic findings associated with a cranial teratoma in two domestic ducks are reported. One tumor arose within the cranial vault and was associated with neurologic signs. The other tumor was subcutaneous and invaded the parietal bone but did not extend into the brain. Both tumors were tridermic.

Hyperimmune bovine colostrum neutralizes Cryptosporidium sporozoites and protects mice against oocyst challenge.

Activity of colostral whey, produced by a cow immunized with oocysts of Cryptosporidium parvum and found to provide prophylaxis against cryptosporidiosis in calves, was tested in 2 experiments. In one experiment BALB/c mice were given the immune whey (HW), whey from a nonimmunized cow (CW), or a balanced salt solution (HBSS) before, during, and after oral inoculation with oocysts of C. parvum. Significantly fewer (P less than 0.05) C. parvum were found in mice that received HW (undiluted, 1:20 or 1:50) than in those treated with similarly diluted CW or with HBSS. In the second experiment it was determined that protection was mediated by specific anti-sporozoite activity when significantly fewer (P less than 0.05) C. parvum were found in mice that received sporozoites treated with HW diluted 1:20 or 1:50 compared with mice that received sporozoites treated with similarly diluted CW or with HBSS.

Red blood cell transfusion practices in very low birth weight infants in 1990s postsurfactant era.

The purposes of this study are (1) to evaluate the practice of red blood cell transfusions in very low birth weight (VLBW) infants (between 501 to 1500 g) during the postsurfactant era of the 1990s; and (2) to evaluate if there is a decreasing trend in red cell transfusions in the 1990s. Database and medical records of VLBW infants admitted to the neonatal intensive care unit (NICU) between January 1990 and December 1995 at Scott & White Clinic, Temple, Texas, were reviewed. Five hundred twenty-seven infants were admitted to the NICU, excluding 5 infants that were transferred out for possible cardiac surgery or for other reasons. Fifty one (9.7%) of these infants died prior to discharge. Hence, data from 476 survivors were reviewed for red blood cell (RBC) transfusions. Transfusions were given at the discretion of the attending neonatologist. None of the infants received erythropoietin. Of the 476 infants, 289 (61%) received RBC transfusions during the hospital stay, with 2.7+/-3.6 transfusions per infant with a volume of 40.5+/-50.4 mL/kg. Smaller infants required significantly more transfusions compared to larger infants when divided into 250-g subgroups. No statistically significant difference was noted in the number of RBC transfusions per infant or number of infants transfused during the 6-year period from year to year. We conclude that VLBW infants in the 1990s postsurfactant era required 2.7 RBC transfusions per infant, on average, with the smallest infants requiring the most transfusions. These data will be helpful to counsel mothers in preterm labor regarding the need of transfusions for each birth weight category. Red cell transfusion practice has not changed over this 6-year period in the 1990s. Additional measures such as erythropoietin or even stricter transfusion criteria may be necessary to decrease transfusions further. However, safety of such measures should be carefully evaluated.

Psychosocial and demographic factors related to health behaviors in the 1st trimester.

OBJECTIVE: To explore the relationship of psychosocial and demographic variables to health behaviors in early pregnancy. DESIGN: First trimester findings presented from a prospective study of weight gain in pregnancy. SETTING: A comprehensive health care system in central Texas. PARTICIPANTS: 114 pregnant women (75% white, 13% African American, 10% Hispanic, 2% Asian) of 12 weeks gestation or less. OUTCOME MEASURE: Self-Care Inventory, which includes diet/eating, substance abuse, recklessness, hygiene-related practices, sleep/rest, and exercise behaviors. RESULTS: In regression analysis the final model of demographic and psychosocial variables showed that higher depressive symptoms, lower internal locus of control for fetal health, and lower family income were related to poorer health behaviors in the 1st trimester of pregnancy. CONCLUSIONS: Health behaviors in early pregnancy may be affected by psychosocial factors such as depressive symptoms. Greater emphasis should be given to such factors in research and prenatal assessments.

Suspected ciliary dysfunction in Chinese Shar Pei pups with pneumonia.

Chronic pneumonia was investigated in a litter of young Chinese Shar Pei in which 4 of 6 dogs were affected. Serum immunoglobulin concentrations (IgA, IgG, IgM) determined by radial immunodiffusion varied over time, but were not consistently lower in affected dogs, compared with control dogs. Two dogs that died had hydrocephalus and lymphoid depletion, in addition to severe broncho-pneumonia. Evaluation of ciliary ultrastructure in 2 affected dogs revealed random orientation of adjacent respiratory tract or oviductal cilia and a greater number of microtubular disarrangements, compared with control dogs. In vivo tracheal mucociliary clearance of 99mtechnetium macroaggregated albumin was absent in 1 dog examined. The ciliary abnormalities were suspected to have resulted in an inefficient mucociliary transport system predisposing to the development of pneumonia. Further evaluation of 1 Chinese Shar Pei revealed lymphocyte mitogenesis results that were not consistently less than those of a control dog, normal total hemolytic complement values, and normal blood neutrophil chemotaxis.

Radiation exposure during cardiology fellowship training.

We report catheterization laboratory personnel dose per case during parallel use of two laboratories from different manufacturers. Initially, four working positions were monitored. Review of the data from the first 140 cases showed a wide range of dose per case. Measurements were then limited to diagnostic coronary angiography cases in which a cardiology fellow was the primary operator. On a per case basis, the dose was higher when a fellow was in the laboratory with pulsed progressive fluoroscopy or was in fellowship year one. The increased dose for first year fellows was more related to increased fluoroscopy time than to cine angiography time. This study emphasizes the importance of close supervision of cardiology fellows early in their training to limit dose to patients and personnel, and it underlines the importance of each catheterization laboratory routinely having the actual personnel dose per case measured.