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Biomedical subjects

J Freeman

Publications and source records attributed to J Freeman.

At least 91 records · Page 5Linked to original sources

Prenatal diagnosis of amniotic band syndrome in a methadone user: review of the literature and a case report.

We present a case and review of the literature of an amniotic band causing malformation in the distal forearm in a baby born to a methadone-dependent mother. This diagnosis was made prenatally at the routine 18-20-week gestation anomaly ultrasound scan. Histology of the amniotic band postpartum revealed hair shafts within its structure. This has not previously been documented, nor has an association of this syndrome with systematic abuse of methadone. The fact that this anomaly could be detected by prenatal ultrasound scanning is of value in the counselling of high-risk pregnancies such as this.

Adult↗

Fetal sexing by ultrasound in the second trimester: maternal preference and professional ability.

The study was planned to determine the proportion of parents that wish to know the sex of their fetus at the 20-week anomaly scan, and to investigate our ability to diagnose correctly the sex of the fetus when undertaken as part of a routine scan. A total of 472 patients gave their informed consent. An attempt was made to identify the genitalia as part of the routine scan. No extra time was allowed to determine the sex of the fetus. Altogether 353 (74.7%) women wanted to know the sex, of which four (0.9%) wanted to know but did not want their partners to know. In 50 (10.6%) cases, it was not possible to determine the fetal sex in the time allowed. When the sex was identified, it was correct in 408 (96.7%) cases, and incorrect in 14 (3.3%) cases. Where the parents wanted to know the sex of the fetus, 24 (6.8%) scans were inconclusive, 319 (97%) were correctly identified, and ten (3%) were incorrectly identified (six male, four female). There were no terminations of pregnancy. The majority of prospective parents wish to know the sex of their child, and, in most cases, it is possible to determine the fetal sex at the time of the routine anomaly scan. During the time allowed, the fetal sex was undetermined in one in ten cases, and 3% were sexed incorrectly. If parents wish to know the gender of their fetus, it would appear reasonable to provide this information, provided that the parents are aware of the failure and error rates of sex identification using ultrasound.

Attitude↗

Embolic stroke in a pregnant patient with a mechanical heart valve on optimal heparin therapy.

A 28-year-old woman with a mechanical aortic heart valve experienced an embolic stroke in early pregnancy after her anticoagulation therapy was changed from warfarin to heparin. This occurred despite use of a subcutaneous heparin infusion pump and optimal anticoagulation. Thromboembolism can occur in pregnant patients with mechanical heart valves despite optimal heparin therapy.

Adult↗

Quantitative epidemiology.

We provide guidance for new practitioners in the vocabulary of modern epidemiology and the application of quantitative methods. Most hospital epidemiology involves surveillance (observational) data that were not part of a planned experiment, so the rubric and logic of controlled experimental studies cannot be applied. Forms of incidence and prevalence often are confused. The names "cohort study" and "case-control study" are unfortunate, as cohort studies rarely involve cohorts and case-control studies allow no active control by the investigator. Either type of study can be prospective or retrospective. Results of studies with discrete outcomes (infected or not, lived or died) often are represented best by a form of the risk ratio with 95% confidence intervals. The potential distorting effects of selection bias, misclassification, and confounding need to be considered.

Cross Infection↗

A university outbreak of gastroenteritis due to a small round-structured virus. Application of molecular diagnostics to identify the etiologic agent and patterns of transmission.

An epidemiologic investigation of a gastroenteritis outbreak in December 1994 indicated that salad consumption during lunch was linked with illness on 2 days (5 December: odds ratio [OR]=3.1, 95% confidence interval [CI]=2.0-5.0; 6 December: OR=3.1, 95% CI=1.9-4.9). Single stool or vomitus specimens from ill students and staff (case-patients) were examined for bacterial and viral pathogens. Small round-structured viruses (SRSVs) were detected by electron microscopy in stool specimens from 9 of 19 case-patients and in vomitus specimens from 3 of 5 case-patients. By reverse transcription-polymerase chain reaction (RT-PCR), the SRSVs were shown to be G-2/P2-B type strain. The nucleotide sequences of RT-PCR products from vomitus and stool specimens of ill students were identical to stool specimens from the ill salad chef. These findings suggest that a single SRSV strain was the etiologic agent in the outbreak that was possibly transmitted to students through consumption of contaminated salad. Epidemiologic investigation in conjunction with molecular diagnostics may enable early identification of sources of infection and improve outbreak control.

Caliciviridae↗

Flap selection in cranial base reconstruction.

We have compared our local, pedicled, and free-flap reconstructions for 90 skull base defects performed over the past 10 years. The pericranial flap was found to provide a reliable dural seal. Free-flap reconstructions exhibited a significantly higher incidence of uncomplicated primary wound healing (95 versus 62.5 percent) and a much lower incidence of flap loss (0 percent), cerebrospinal fluid leak (5 percent), meningitis, and abscess (0 percent) when compared with defects reconstructed with pedicled myocutaneous flaps. We conclude that microvascular free-tissue transfer is the safest, most economical procedure when faced with moderate to large composite defects of the cranial base.

Female↗

Repeated verbal interruptions during exposure to complex transcerebral magnetic fields elicit irritability: implications for opiate effects.

Men (n = 17) and women (n = 18) listened to a brief narrative and then were exposed for 30 min. to a control condition or to a weak (1 microTesla) complex magnetic field applied over the left hemisphere, the right hemisphere, or bilaterally. The subjects were interrupted intermittently to report their thoughts during this period. Because the wave structure of the field had been shown to elevate nociceptive thresholds and to simulate the effects of morphine in rats, we predicted that the group who received the bilateral stimulation should report greater irritability because of their disrupted pleasant experiences. The results supported this hypothesis.

Adult↗

A randomized trial comparing 1.25 mmol/l calcium dialysate to 1.75 mmol/l calcium dialysate in CAPD patients.

BACKGROUND: Effective control of hyperparathyroidism and renal osteodystrophy in CAPD patients requires a combination of calcitriol and calcium carbonate (CaCO3), but is frequently limited by hypercalcaemia. Reducing dialysate calcium (Ca) concentration may overcome this problem, but had not been examined in a controlled trial. METHODS: 45 stable CAPD patients were randomly assigned in a prospective double-blind trial to either a study group (1.25 mmol/l Ca dialysate) or a control group (1.75 mmol/l Ca dialysate) for 12 months. Clinical, biochemical and radiological parameters of secondary hyperparathyroidism were followed. RESULTS: Twenty-three patients did not complete the study due to death (9), transplantation (7) or conversion to haemodialysis (7). Eleven patients in each group completed the study. Mean serum Ca, phosphate, ionized Ca, aluminium, alkaline phosphatase (AP), and bone mineral density (BMD) Z-scores did not differ significantly at any time within or between the two groups. Severe hypercalcaemia was more common in the control group (11 vs. 2, P = 0.027). Mean serum intact parathyroid hormone (PTH) and osteocalcin (OCN) initially rose in the study group relative to controls at 3 months (40 +/- 7 vs 12 +/- 3 pmol/l, P = 0.004, and 33 +/- 5 vs 15 +/- 2 micrograms/l, P = 0.002 respectively), but were not sustained. Median weekly dosages of calcitriol and daily dosages of CaCO3 increased significantly in the study group (O microgram to 1 microgram P = 0.014 and 1260 mg to 2520 mg P = 0.002 respectively), but not in the control group. Supplementary aluminium hydroxide (A1, (OH)3) was required for phosphate control in both study (n = 5) and control patients (n = 4). CONCLUSIONS: Lowering dialysate calcium concentration reduced the frequency of severe hypercalcaemia and allowed prescription of larger quantities of calcitriol and CaCO3. However, in this study it offered no advantage in terms of A1(OH)3 requirement, while bone mass density did and may have initially exacerbated secondary hyperparathyroidism not change.

Aluminum Hydroxide↗

Injured stable knee with acute effusion: MRI evaluation.

This study was done to evaluate the magnetic resonance imaging (MRI) findings in acute traumatic effusions of the knee without ligament instability or radiographic abnormality other than the effusion. On reviewing the charts of 927 patients who had MRI of the knee, we found 114 patients who met the following criteria for inclusion in this study: (1) acute effusion by examination or history, (2) ligament stability on examination, and (3) normal findings on radiographs (excluding effusion). The total of 144 pathologic diagnoses made by MRI included bone injury (53%), disruption of the anterior cruciate ligament (19%), sprain of the medial collateral ligament (12%), medial meniscus tear (11%), lateral meniscus tear (5%), and rupture of the posterior cruciate ligament ( < 1%). Eight studies (7%) were read as normal. These MRI data are significantly different from data of previous studies using arthroscopy to evaluate acute knee injuries without ligament instability. The findings more accurately reflect the injury pattern seen in this setting because MRI can show both bone and soft tissue injury. From this study, we conclude that bone injury is the most common cause of acute effusion in the patient with ligament stability and normal radiographs.

Adolescent↗

The effect of whole-body irradiation of nude mice on the tumor transplantability and control probability of a human soft tissue sarcoma xenograft.

This study has evaluated the impact of the suppression and recovery of the residual immunity in NCr/Sed nude (nu/nu) mice after whole-body irradiation using xenotransplantability and tumor control probability as the end points. For this investigation the xenograft was a human soft tissue sarcoma (HSTS26T). Two assays, the TD50 (the number of tumor cells required to induce a tumor in 50% of the recipients) and the TCD50 (the radiation dose required to control 50% of tumors) were used. For TD50 assays, tumor cells were injected subcutaneously (sc) into the legs of control and whole-body- irradiated nude mice at 1 day or 4, 8 or 12 weeks after irradiation. For TCD50 assays, tumors were transplanted sc into the legs of nude mice which had not been irradiated or which had been given whole-body irradiation at 1 day or 12 weeks prior to transplantation. The tumors were given single-dose irradiation when they reached 6 mm mean diameter under clamp-hypoxic conditions. The results show that the TD50's of mice receiving the injection 1 day and 4 and 8 weeks after whole-body irradiation were 3.6 to >100 times lower than that of unirradiated mice. Two groups which showed a statistically significant difference in TD50 's were those which received the injection 1 day and 8 weeks after whole-body irradiation (P < 0.01 and P < 0.05, respectively). No difference was found in TD50 values between mice that received injection 12 weeks after whole-body irradiation and those which were not irradiated. The TCD50 values of tumors in nonirradiated mice and in mice which had received whole-body irradiation 1 day and 12 weeks prior to to transplantation were 26.8, 44.1 and 33.9 Gy, respectively. Significantly lower TCD50 values were found in groups of nonirradiated mice or mice which received whole-body irradiation 12 weeks prior to transplantation in comparison with the group of mice that received whole-body irradiation on day 1 (both P < 0.05). No significant difference was found between the TCD50 values of the group of mice that received whole-body irradiation 12 weeks prior to transplantation and those for nonirradiated controls. Our conclusion is that the whole-body irradiation can enhance the transplantability of the HSTS26T tumor in nude mice significantly; this enhancing effect will decrease to the pre-irradiation level by 12 weeks after whole-body irradiation. Also, the suppression and recovery of residual immunity after whole-body irradiation can influence the TCD50 values of the same tumor xenografts in nude mice significantly. The changes in TD50 and TCD50 values correlate with the depletion and recovery of the total splenic lymphoid cell number, and especially in natural killer cell activity. We recommend that further immunosuppression in nude mice is necessary when using this model system for studies of human tumors.

Animals↗

Surgery with adjuvant irradiation in patients with pathologic stage C adenocarcinoma of the prostate.

BACKGROUND: In recent years, the routine use of prostate-specific antigen (PSA) to detect cancer of the prostate (CaP) early has renewed the controversy regarding radiotherapy versus radical prostatectomy as the superior definitive treatment. Radiotherapy alone has been reported to result in a high incidence of local recurrence, whereas on the other hand surgical treatment has resulted in a high incidence of microscopic residual tumor. The purpose of this study was to review our treatment results with radical prostatectomy followed by planned courses of postoperative irradiation in patients with pathologic Stage (PS) C disease. METHODS: From 1972 to 1989, 95 patients with CaP with PS C tumors were treated with radical prostatectomy and bilateral pelvic lymphadenectomy. Pathologic stage distribution was: C1 in 26 (27%), C2 in 37 (39%), and C3 in 32 (34%) patients. The median follow-up was 6 years. All 95 study patients received postoperative pelvic irradiation as the only adjuvant treatment. Radiotherapy treated volume included the prostatic fossa and its immediate vicinity. The RT dose ranged from 33 Gy to 61.8 Gy (median, 45 Gy). RESULTS: The overall 5- and 10-year actuarial survival rates were 94% and 73%, respectively, with the 5 and 10 year disease specific survival of 98% and 91%, respectively. Clinical and/or prostate specific antigen recurrence was 31% at 5 years and 44% at 10 years. Prostate specific antigen elevation without clinical evidence of recurrent disease was recorded in 26 (27%) patients. Seminal vesicle involvement (C3) and high Gleason's score (8-10) were the most important factors predicting recurrence. Of the 95 patients treated, 2 had pelvic recurrence alone and 1 had local and distant metastatic disease. Radiotherapy was well tolerated with no clinically important morbidity. CONCLUSION: Based on this experience, moderate dose adjuvant radiotherapy after radical prostatectomy in patients with PS C CaP is recommended.

Adenocarcinoma↗

A majority of inverted sinonasal papillomas carries Epstein-Barr virus genomes.

BACKGROUND: The relationship between sinonasal inverted papilloma (IP) and various strains of human papilloma virus (HPV) has been examined previously. Yet there is little consensus regarding the incidence or role of HPV in IP. The possible role of Epstein-Barr virus (EBV), which, like HPV, is a DNA virus linked to human lymphoid and epithelial malignancies, was investigated. METHODS: The polymerase chain reaction (PCR) was used to detect EBV genomic sequences in surgical specimens of IP, in benign nasal polyps, and various control tissues. The IP specimens were similarly examined for the presence of HPV types 6, 11, 16, and 18. RESULTS: EBV DNA was found in 13 of 20 IP specimens (65%) and none of the 10 control tissues. Nine of the 20 specimens contained HPV DNA, and 5 of 20 specimens contained both EBV and HPV. CONCLUSIONS: These results imply a previously unsuspected role for Epstein-Barr virus in the pathogenesis of sinonasal inverted papilloma.

DNA, Viral↗

The effect of combining recombinant human tumor necrosis factor-alpha with local radiation on tumor control probability of a human glioblastoma multiforme xenograft in nude mice.

PURPOSE: To evaluate the antitumor activity of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) on a human glioblastoma multiforme (U87) xenograft in nude mice, and to study the effect of combining rHuTNF-alpha with local radiation on the tumor control probability of this tumor model. METHODS AND MATERIALS: U87 xenograft was transplanted SC into the right hindleg of NCr/Sed nude mice (7-8 weeks old, male). When tumors reached a volume of about 110 mm3, mice were randomly assigned to treatment: rHuTNF-alpha alone compared with normal saline control; or local radiation plus rHuTNF-alpha vs. local radiation plus normal saline. Parameters of growth delay, volume doubling time, percentage of necrosis, and cell loss factor were used to assess the antitumor effects of rHuTNF-alpha on this tumor. The TCD50 (tumor control dose 50%) was used as an endpoint to determine the effect of combining rHuTNF-alpha with local radiation. RESULTS: Tumor growth in mice treated with a dose of 150 micrograms/kg body weight rHuTNF-alpha, IP injection daily for 7 consecutive days, was delayed about 8 days compared to that in controls. Tumors in the treatment group had a significantly longer volume doubling time, and were smaller in volume and more necrotic than matched tumors in control group. rHuTNF-alpha also induced a 2.3 times increase of cell loss factor. The administration of the above-mentioned dose of rHuTNF-alpha starting 24 h after single doses of localized irradiation under hypoxic condition, resulted in a significant reduction in TCD50 from the control value of 60.9 Gy to 50.5 Gy (p < 0.01). CONCLUSION: rHuTNF-alpha exhibits an antitumor effect against U87 xenograft in nude mice, as evidenced by an increased delay in tumor growth as well as cell loss factor. Also, there was an augmentation of tumor curability when given in combination with radiotherapy, resulting in a significantly lower TCD50 value in the treatment vs. the control groups.

Animals↗

In vivo radiation sensitivity of glioblastoma multiforme.

PURPOSE: Human glioblastoma (GBM) is one of the most resistant tumors to radiation. In previous reports, we have demonstrated a wide range of radiation sensitivity of GBM in vitro; that is, SF2 values of 0.2 to 0.8. The great sensitivity of some of the cell lines is not in accord with the almost invariably fatal clinical outcome of patients with GBM. The sensitivity of cells in vitro pertains to cells cultured in optimal nutritional conditions. The TCD50 (the radiation dose necessary to control 50% of the tumors locally) determined in lab animals is analogous to the use of radiation with curative intent in clinical radiation oncology. The aim of the present study was (a) to evaluate the sensitivity of GBM in vivo relative to that of other tumor types and (b) assess the relationship between the single dose TCD50 of the xenografts and the sensitivity of the corresponding cell lines in vitro. METHODS AND MATERIALS: The TCD50 assay was used to study twelve human tumor lines. Four previously published values were added. A total of 10 GBM, 4 squamous cell carcinoma (SCC), 1 soft tissue sarcoma (STS), and 1 cancer colon (CC) are included in the analysis. For further suppression of the residual immune system, all the animals received 6 Gy whole-body irradiation 1 day before transplantation. Local tumor irradiations were given as a single dose, under conditions of clamp hypoxia using a Cs irradiator. RESULTS: The TCD50 values for the 10 GBM xenografts varied between 32.5 and 75.2 Gy, with an average of 47.2 +/- 13.1 Gy. The TCD50 values for the SCC were similar to those of the GBM and ranged from 40.7 and 54.4 Gy, with a mean of 46.8 +/- 6.4. The difference between the average TCD50 of GBM and SCC was not significant. The STS and CC xenografts had TCD50 values of 46.0 and 49.2 Gy, respectively. No correlation was found between the TCD50 in vivo and the SF2 or D0 in vitro. CONCLUSIONS: Our data on GBM xenografts showed a wide range of sensitivities to single dose irradiation in vivo, which does not correlate with the almost invariably fatal clinical outcome of these patients. No correlation was observed between the TCD50 in vivo and the in vitro SF2/D0 of the corresponding cell lines. Our in vivo and in vitro data on GBM suggest that radiation sensitivity alone does not explain the cause of the poor clinical response of GBM to radiation, and other factors could contribute to this response.

Animals↗

The effect of the overall treatment time of fractionated irradiation on the tumor control probability of a human soft tissue sarcoma xenograft in nude mice.

PURPOSE: To study the impact of the overall treatment time of fractionated irradiation on the tumor control probability (TCP) of a human soft tissue sarcoma xenograft growing in nude mice, as well as to compare the pretreatment potential doubling time (Tpot) of this tumor to the effective doubling time (Teff) derived from three different schedules of irradiation using the same total number of fractions with different overall treatment times. METHODS AND MATERIALS: The TCP was assessed using the TCD50 value (the 50% tumor control dose) as an end point. A total of 240 male nude mice, 7-8 weeks old were used in three experimental groups that received the same total number of fractions (30 fractions) with different overall treatment times. In group 1, the animals received three equal fractions/day for 10 consecutive days, in group 2 they received two equal fractions/day for 15 consecutive days, and in group 3 one fraction/day for 30 consecutive days. All irradiations were given under normal blood flow conditions to air breathing animals. The mean tumor diameter at the start of irradiation was 7-8 mm. The mean interfraction intervals were from 8-24 h. The Tpot was measured using Iododeoxyuridine (IudR) labeling and flow cytometry and was compared to Teff. RESULTS: The TCD50 values of the three different treatment schedules were 58.8 Gy, 63.2 Gy, and 75.6 Gy for groups 1, 2, and 3, respectively. This difference in TCD50 values was significant (p < 0.05) between groups 1 and 2 (30 fractions/10 days and 30 fractions/15 days) vs. group 3 (30 fractions/30 days). The loss in TCP due to the prolongation of the overall treatment time from 10 days to 30 days was found to be 1.35-1.4 Gy/day. The pretreatment Tpot (2.4 days) was longer than the calculated Teff in groups 2 and 3 (1.35 days). CONCLUSION: Our data show a significant loss in TCP with prolongation of the overall treatment time. This is most probably due to an accelerated repopulation of tumor clonogens. The pretreatment Tpot of this tumor model does not reflect the actual doubling of the clonogens in a protracted regimen.

Animals↗

Quantitative comparison of xenotransplantation of a human soft tissue sarcoma into the subcutaneous tissue of normal, postincision, and postincision plus indomethacin-treated nude mice.

The purpose of this study was to test the hypotheses that (1) surgical wounding can enhance the xenotransplantability of a human soft tissue sarcoma (HSTS26T) into subcutaneous (s.c.) tissue of nude mice, and (2) Indomethacin may reduce the xenotransplantability of this human tumor in the surgical wounding animal model by suppressing angiogenesis. The experimental method was to employ the quantitative transplantation assays (TD50, the number of tumor cells that, on average, would be expected to induce a tumor in 50% of the recipients). After an incisional wound (1.0-1.2 cm long) was made on the right leg of each experimental mouse, tumor cells were inoculated into the surgical wound, or into the contralateral leg at 24 and 72 hr postincision, and in another group tumor cells were inoculated into the wound at 72 hr postincision, plus daily s.c. injection of indomethacin, 2 mg/kg body weight for 8 consecutive days in a separate experiment. Nonincisional mice received the same inoculation as the control groups. The TD50s of surgically wounded groups were 3.5-10.7 times lower than that of the control groups. Significantly lower TD50 values were found in groups of cells inoculated into the surgical wound at 72 hr postincision (P < 0.05 or P < 0.01) and into the contralateral leg at 24 hr postincision (P = 0.05). No significant difference was found between the TD50 values in mice that received cells inoculated at 72 hr postincision plus indomethacin treatment, and those with no wound controls. Our conclusion is that the surgical wound can enhance the xenotransplantability of HSTS26T in nude mice. Indomethacin can decrease this enhancing effect level similar to that in no-wound controls and may prevent tumor recurrence in a surgical wound.

Animals↗

Speech-language outcomes of hemispherectomy in children and young adults.

Children and young adults who had undergone right or left hemispherectomy for intractable seizures after a period of normal language acquisition were compared with respect to scores on speech and language tests. The majority of the subjects had full scale IQs in the borderline to mentally retarded range. Language scores were computed in relation to estimated mental age, not chronological age. On this basis, the left hemispherectomized children were more likely to show syntactic comprehension and rapid-rate auditory processing deficits than the right hemispherectomized. The two groups were similar to one another and to normal children in speech production. The findings are discussed in relation to developmental language disorders.

Adolescent↗

In vitro cytolytic activity of lymphocytes from tumor-draining lymph nodes is associated with increased numbers of CD8+ cells and increased cytokine production.

A murine footpad tumor model was used to determine the cytotoxic activity, tumor specificity, phenotypic profile, and cytokine production of stimulated cells from draining lymph nodes (DLN). Popliteal DLN from 5-day-old P-815 footpad tumors were stimulated with 10(-7) M phorbol 12, 13-dibutyrate +5 x 10(-7) M ionomycin for 16 hr and cultured in IL-2 (20 units/ml) for 7 or 14 days without autologous tumor. Most cells in both groups were CD3+ (93% at Day 7, 99% at Day 14); however, the percentage of CD8+ cells increased as the cell population matured in the presence of low-dose IL-2. On Day 7, the phenotypic profile was 62% CD4+ and 29% CD8+, whereas on Day 14 it was 16% CD4+ and 81% CD8+. Similarly, in vitro cytokine production increased with time in culture. After 7 days, the level of tumor necrosis factor-alpha (TNF-alpha) was 220 pg/mL and the interferon-gamma (IF-gamma) production was 150 pg/ml. At Day 14 the TNF level had increased to 500 pg/ml, and IF production had increased to 350 pg/ml. These increases in the CD8+ population and in cytokine production correlated with the increase in the percentage of target cells killed by the DLN cells. Cytolytic activity against P-815 was only 13% on Day 7 but 39% on Day 14. Neither group of effector cells (Day 7 or Day 14) had any cytolytic activity against the syngeneic tumor cell line L-1210, demonstrating the tumor specificity of the DLN cells. We describe a model for generating tumor-specific cytotoxic T-cells that have significant cytokine production, which may account for previously described in vivo activity.

Animals↗