Biomedical subjects

J C Kennedy

Publications and source records attributed to J C Kennedy.

At least 37 records · Page 2Linked to original sources

PubMed1993

Pyloric stenosis: the Christchurch experience.

OBJECT: Evaluation of the performance of a general paediatric unit in diagnosis and treatment of infantile hypertrophic pyloric stenosis, including morbidity and measurable outcomes in relationship to changing management. METHODS: Retrospective case note audit. RESULTS: In the 11 year period 1980-91, 103 infants underwent surgical correction of pyloric stenosis, after correction of metabolic disturbance. There was a predominance of males (82.5%), but the incidence of first born infants affected was no greater than the population birth order. While the clinical diagnosis was firm in the majority of infants, over 75% had at least one radiologic imaging procedure. On objective criteria, 80% of patients were less than 5% dehydrated, despite having electrolyte and acid-base derangement. The relatively high incidence of mucosal perforation (31.1%) did not lead to further morbidity. The incidence of postoperative vomiting (19.4%) was significantly less than in previously reported series. There were no deaths, one patient suffered longterm neurologic deficit following profound hypoglycaemia. A change in preoperative management to aggressive rehydration did not reduce morbidity, and was associated with an increased median postoperative stay. CONCLUSIONS: Pyloric stenosis remains a relatively common surgical problem of infancy. The cornerstone of diagnosis remains a clinical one; however there is a place for radiology. Operative repair is elective, following correction of metabolic derangement. In a general paediatric unit, long term sequelae of initial morbidity are rare.

Body Weight↗

PubMed1993

Evidence of lasting functional destruction of the rat endometrium after 5-aminolevulinic acid-induced photodynamic ablation: prevention of implantation.

OBJECTIVE: We evaluated disruption of endometrial function after treatment with 5-aminolevulinic acid with or without light exposure. STUDY DESIGN: In a conventional laboratory setting adult Sprague-Dawley female rats were treated with various doses of 5-aminolevulinic acid in one uterine horn and saline in the contralateral horn. Three hours after treatment both uterine horns were exposed to light, and the rats were bred to a fertile male 10 or 60 days later. Ablation of endometrium was evaluated by both rate of implantation and histologic features. RESULTS: In the absence of light exposure 5-aminolevulinic acid had no significant effect on the rate of implantation, compared with saline (76% vs 92%, n = 25, p > 0.05). In contrast, 5-aminolevulinic acid treatment plus light exposure profoundly decreased the rate of implantation in the 5-aminolevulinic acid-treated uterine horns of rats bred 10 days (3.8% vs 100%, n = 26, p < 0.001) or 60 days after treatment (16.7% vs 100%, n = 24, p < 0.001). Histologic examination revealed that the 5-aminolevulinic acid plus light-treated uterine horns were completely devoid of endometrium. CONCLUSION: Photodynamic treatment with 5-aminolevulinic acid resulted in a persistent disruption of rat endometrial function and was consistent with the histologic evidence of complete endometrial ablation. In addition, a partial destruction of myometrium adjacent to endometrium was observed. The myometrial damage may be through a nonphotodynamic mechanism because myometrium is unable to synthesize protoporphyrin IX from 5-aminolevulinic acid.

Aminolevulinic Acid↗

PubMed1993

Intrauterine 5-aminolevulinic acid induces selective fluorescence and photodynamic ablation of the rat endometrium.

5-Aminolevulinic acid (ALA), a precursor of protoporphyrin IX (Pp IX), was administered into the rat uterine cavity in an attempt to selectively ablate the endometrium. Doses of ALA ranging from 4 to 50 mg were injected into one uterine horn of rats while the vehicle (saline) was injected into the contralateral horn. Animals were divided into three groups. In group one, the uterine horns were removed and processed for either fluorescent microscopy or spectrophotofluorometry 3 h later. In group two, rats were allowed to survive for either 2 or 10 days, and then the uterine horns were harvested and processed histologically. In group three, both uterine horns were exposed to transmural light (approximately 150 J/cm2) 3 h after administration of ALA or saline and processed histologically either 2 or 10 days later. Fluorescent microscopy showed fluorescence in the endometrium and not in the myometrium. The maximum emission spectra of endometrial fluorescence occurred at 630 and 690 nm, characteristic of Pp IX. In contrast, no fluorescence was detected in saline-treated uterine horns. Light exposure resulted in extensive damage only to the ALA-treated endometrium. There was no indication of regeneration 10 days after treatment. We conclude from these studies that ALA administered into the lumen of the rat uterus is selectively converted into Pp IX within the endometrium. Furthermore, photoactivation of the Pp IX results in selective ablation of the endometrium.

Aminolevulinic Acid↗

PubMed1993

Pulsatile luteinizing hormone patterns in long term oral contraceptive users.

Oral contraceptives (OC) inhibit folliculogenesis by a central suppressive action on the release of gonadotropins. To characterize the nature of these central effects, we studied 40 long term OC users on 3 different OCs: two monophasic preparations with 30 micrograms ethinyl estradiol and 150 micrograms l-norgestrel (group 1; n = 15), 150 micrograms desogestrel (group 2; n = 10), and a triphasic formulation containing 30-40 micrograms ethinyl estradiol and 50, 75, and 125 micrograms l-norgestrel (group 3; n = 15). Blood sampling at 10-min intervals during 6-h periods was performed at different moments in the pill cycle. Thirteen healthy volunteers with regular ovulatory cycles served as normal controls. FSH and LH were measured by a sensitive immunoradiometric assay. Pulsatile LH release was observed in all OC users. Mean serum LH and FSH levels, number of LH pulses per 6 h, and the amplitude of LH pulses on day 1 of the pill cycle did not differ from early follicular phase control values. FSH levels were rapidly suppressed from day 2 onward in all three groups, whereas LH levels progressively declined in groups 1 and 2 from day 8 onward. In group 3, however, LH levels were only significantly suppressed after day 13. The number of LH pulses per 6 h decreased in all groups starting on day 2, whereas the amplitude of LH pulses increased. A substantial percentage of LH pulses observed in OC users after day 1 were of low amplitude (< 0.75 IU/L). From these results, we conclude that 1) pulsatile release of LH is maintained during OC use; 2) FSH levels are suppressed equally early and equally effective by all OCs studied; 3) during OC use, the number of LH pulses per 6 h is reduced; 4) modulation of LH pulse amplitudes, and subsequently of serum LH levels, is mainly mediated by a dose- and time-dependent effect of the gestagenic component of the OC; and 5) after the 7-day pill-free interval, a normal early follicular phase pulse pattern is found, even in long term OC users, suggesting that in this period, most of the steroidogenic feedback effects wear off.

Adult↗

PubMed1993

Pulsatile luteinizing hormone secretion during the first and the fourth cycle on two different oral contraceptives containing gestodene.

Oral contraceptives inhibit ovarian follicular growth by suppressing the release of gonadotropins from the pituitary. We studied basal and gonadotropin-releasing hormone-stimulated gonadotropin release, as well as pulsatile luteinizing hormone (LH) secretion, in ten healthy volunteers who had not used oral contraceptives before. Subjects received either a monophasic preparation containing 30 micrograms of ethinylestradiol and 75 micrograms of gestodene (group 1) or a triphasic formulation containing 30-40 micrograms of ethinylestradiol and 50, 70 and 100 micrograms of gestodene (group 2). Blood sampling at 10-min intervals during 6-h periods was performed on days 1, 8, 15 and 21 of both the first and fourth pill cycle. Thirteen healthy volunteers with regular ovulatory cycles served as normal controls. Both LH and follicle-stimulating hormone (FSH) were measured by a sensitive immunoradiometric assay. Pulsatile LH secretion was observed in all oral contraceptive users. Mean serum LH and FSH levels, number of pulses/6 h and the amplitude of LH pulses on day 1 in both the first and fourth pill cycle did not differ from early follicular phase controls in both groups. The FSH levels were suppressed rapidly in both groups, even in first cycles, while LH serum levels progressively declined in all cycles studied. In both groups, amplitudes of LH pulses decreased from day 8 onwards, with a substantial number of low-amplitude pulses (< 0.75 U/l) interspersed between large-amplitude pulses. On day 1 of the fourth pill cycle a significant number of pulses were of low amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

The effects of levonorgestrel, desogestrel and gestodene on the pulsatile release of luteinizing hormone in oral contraceptive users.

The dynamics of luteinizing hormone (LH) and follicle stimulating hormone (FSH) release were investigated in 60 long-term oral contraceptive (OC) users. Five different types of OC, all containing the same amount of estrogens were studied: three monophasic preparations containing levonorgestrel, desogestrel and gestodene, respectively, and two triphasic formulations, containing levonorgestrel or gestodene. Thirteen healthy, normally cycling volunteers served as controls. Blood sampling was performed at 10-min intervals during a 6-h period to determine the pulsatile release of LH. LH and FSH were measured using a sensitive immunoradiometric assay. Pulse patterns were classified on the basis of the overall LH level, as well as on the character of the LH pulses, according to both frequency and amplitude characteristics. Pulsatile LH release was maintained during OC use. After the 7-day pill-free interval, FSH levels as well as the LH pulse patterns were comparable to those of early follicular-phase controls. FSH levels and FSH release in response to a gonadotropin releasing hormone (GnRH) challenge were profoundly suppressed in all OC users, as early as day 8 of the pill cycle. LH release during the pill cycle was characterized by either a low frequency (median 1 pulse/6 h), high amplitude (median 2.5 IU/l) pulse pattern or by a pattern of low-amplitude pulses (median 0.2 IU/l) and low basal LH levels (median 0.2 IU/l). The distribution of these pulse patterns showed marked differences between different OC preparations and depended on both the type and dose regimen of the gestagenic component of the OC.

Adult↗

PubMed1993

Primary adenocarcinoma of the vulva, possibly cloacogenic. A report of two cases.

Primary adenocarcinoma of the vulva, arising in continuity with the epidermis and unrelated to the underlying mucus glands, is a distinctly uncommon neoplasm. The origin of such an unusual tumor, although attributed to cloacal remnants, remains speculative. We describe two patients with this rare lesion. No other primary tumor was found in either of the two after a thorough investigation. One patient was treated with radical vulvectomy and was free of disease for 10 years, until her death from unrelated causes. The second patient was treated with wide local excision and was free of disease four years postoperatively. Our experience indicates the need to recognize this tumor as a primary and not metastatic neoplasm of the vulva. We also noticed that in both cases, despite its histologic malignancy and ulceration, the tumor was superficial in its extent and without any tendency for deeper invasion. It can therefore be treated effectively with wide local excision, thus eliminating the need for radical vulvectomy.

Adenocarcinoma↗

PubMed1992

Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy.

The tissue photosensitizer protoporphyrin IX (PpIX) is an immediate precursor of heme in the biosynthetic pathway for heme. In certain types of cells and tissues, the rate of synthesis of PpIX is determined by the rate of synthesis of 5-aminolevulinic acid (ALA), which in turn is regulated via a feedback control mechanism governed by the concentration of free heme. The presence of exogenous ALA bypasses the feedback control, and thus may induce the intracellular accumulation of photosensitizing concentrations of PpIX. However, this occurs only in certain types of cells and tissues. The resulting tissue-specific photosensitization provides a basis for using ALA-induced PpIX for photodynamic therapy. The topical application of ALA to certain malignant and non-malignant lesions of the skin can induce a clinically useful degree of lesion-specific photosensitization. Superficial basal cell carcinomas showed a complete response rate of approximately 79% following a single exposure to light. Recent preclinical studies in experimental animals and human volunteers indicate that ALA can induce a localized tissue-specific photosensitization if administered by intradermal injection. A generalized but still quite tissue-specific photosensitization may be induced if ALA is administered by either subcutaneous or intraperitoneal injection or by mouth. This opens the possibility of using ALA-induced PpIX to treat tumors that are too thick or that lie too deep to be accessible to either topical or locally injected ALA.

Aminolevulinic Acid↗

PubMed1992

Flow cytometric DNA analysis of ovarian Brenner tumors and transitional cell carcinomas.

Flow cytometry has been previously used as a method of obtaining prognostic information about ovarian carcinomas using ploidy, DNA index, and S-phase fraction. DNA content has also been assessed in ovarian tumors of low malignant potential. Brenner tumor variants such as metaplastic, proliferating, and low malignant potential, recently designated as intermediate Brenner tumors, and malignant Brenner tumors are unusual tumors that present classification problems. Their histological appearance may not accurately reflect biological activity. We used flow cytometry to analyze paraffin-embedded tissue for DNA content and S-phase in 34 Brenner tumors, three ovarian transitional cell (urothelial) carcinomas (TCCs), and nine normal control ovaries. We correlated histological and clinical features with DNA analysis. Twenty-five Brenner tumors and three ovarian TCCs were acceptable for histogram analysis (coefficient of variation less than 7.0). Thirteen typical, three metaplastic (extensive mucinous or glandular metaplasia), and two proliferating (papillary formation with increased cellularity) Brenner tumors were diploid. One proliferating tumor was tetraploid. The single Brenner tumor of low malignant potential was diploid but had an increased S-phase. Four of five malignant Brenner tumors were aneuploid, and one was diploid. All the TCCs were aneuploid. S-phase was elevated in intermediate and malignant Brenner tumors and TCC. Limited numbers of cases available preclude prognostic prediction based on ploidy in malignant Brenner tumors or primary ovarian TCCs. DNA ploidy and S-phase reflect the intermediate status of metaplastic, proliferating, and low malignant potential Brenner tumors.

Adult↗

PubMed1992

Prognosis in fetal cystic hygroma.

Axillary and lateral cervical fetal cystic hygromas in a fetus with normal karyotype are described. Fetal death at 25 weeks' gestation occurred. A literature review revealed that for cystic hygroma 42% of infants are 45XO, 38% have a normal karyotype, and 18% have trisomies. Prognosis is grim if the karyotype is abnormal or if hydrops or bilateral pleural effusions are present. Survival rate progressively improves with normal karyotype (27%), unilateral pleural effusion (40%), atypical location (56%), and resolution of cystic hygroma (71%). No single feature signifies 100% survival. The overall survival rate for fetal cystic hygroma is 10%. Prognosis remains guarded regardless of all other factors until the fetus reaches 26 weeks' gestation, after which time a 67% chance of ultimate survival can be expected. Only 42% of documented survivors were completely normal at follow-up.

Axilla↗

PubMed1992

Comparison of cell proliferation in breast carcinoma using image analysis (Ki-67) and flow cytometric systems.

Cellular proliferation has been implicated as an important predictor of biologic behavior in breast cancer. Cellular proliferation of 95 breast carcinomas was evaluated by comparing Ki-67 immunoreactivity in frozen sections quantitated by image analysis with S-phase and S + G2/M phase fraction determined by flow cytometry on nuclei extracted from fixed, paraffin-embedded sections (modified Hedley's technique). These parameters were correlated with traditional morphologic features of histologic grade, including mitotic count. Ki-67 immunoreactivity correlated with S-phase fraction determined by flow cytometry (r = .41, P = .001) and with S + G2/M phase fraction determined by flow cytometry (r = .29, P = .008). There was also a correlation between histologic grade and Ki-67 immunoreactivity (r = .30, P = .004) and between histologic grade and S-phase fraction (r = .42, P = .0001). Mitotic count correlated with Ki-67 immunoreactivity (r = .25, P = .015) and with S-phase fraction (r = .35, P = .001). Image and flow cytometric analysis systems provide comparable measurements of cellular proliferation; their measurements correlate with histologic grade and mitotic count in breast cancer.

Breast Neoplasms↗

PubMed1992

Primary carcinoid tumor of the urinary bladder.

A 62-year-old woman who presented with urinary frequency and microscopic hematuria was found to have a 1.2 x 1.0 x 0.6-cm polypoid carcinoid tumor of the urinary bladder. The tissue resected from the base after removal of the polypoid lesion disclosed a small focus of residual carcinoid tumor, associated with Brunn's epithelial nests, cystitis cystica, and cystitis glandularis. Tumor cells exhibited strong argyrophilia and weak argentaffinity. Immunohistochemical staining reactions were strongly positive for chromogranin and serotonin, and electron microscopy revealed characteristic dense-core granules. Flow cytometric evaluation revealed an aneuploid cell population with a DNA index of 1.20.

Carcinoid Tumor↗

PubMed1992

Clearance times of porphyrin derivatives from mice as measured by in vivo fluorescence spectroscopy.

The clearance times of 17 different porphyrin derivatives from SKH:HR-1 mice have been measured using the technique of in vivo fluorescence spectroscopy. This technique monitors the in vivo porphyrin fluorescence observed from the external skin surface. Most hydrophilic porphyrin derivatives show relatively short clearance times, in the order of 2.5-6 h. The dicarboxylic acid porphyrins, proto-, hydroxyethylvinyldeutero- and hematoporphyrin IX have clearance times of 7.8, 12.2 and 14.7 h respectively. The mixture hematoporphyrin derivative has an intermediate clearance time of 12.6 h. N-methylated porphyrins show clearance times in the vicinity of 15-22 h. Monoaspartyl chlorin e6 shows the longest clearance time of all porphyrin derivatives measured (30.3 h).

Animals↗

PubMed1991

A comparison of fluorescence methods used in the pharmacokinetic studies of Zn(II)phthalocyanine in mice.

The pharmacokinetics of Zn phthalocyanine (ZnPc) encapsulated in dipalmitoyl-phosphatidylcholine (DPPC) liposomes, injected intravenously in Skh:HR-1 nude mice, was monitored by two in vitro techniques and one in vivo technique, all based on fluorescence spectroscopy. The in vitro methods involve either fluorescence measurements on thin tissue sections or on extracts from these tissues. The in vivo method involves the fluorescence measurement at the skin surface. Both in vitro techniques gave similar results which are consistent with previous findings on the pharmacokinetic behavior of ZnPc. The liver and spleen showed rapid ZnPc concentration increases, reaching a maximum level in 30 min. or less post drug administration. Relatively little ZnPc was detected in the skin, fat or muscle, the maximum concentration occurring at 12 h. In vivo fluorescence reached a maximum intensity approx. 6 h post injection at the mid-chest analysis site and at 12 h in the thigh. The in vivo measurements at two different anatomical sites showed pharmacokinetic behavior that reflects an overall integrated fluorescence originating from several tissue sites.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1991

Semiautomation of preparation of fixed paraffin-embedded tissue for DNA analysis.

The usual manual preparation of single-cell suspensions from fixed paraffin-embedded tissue sections for flow cytometric (FCM) DNA ploidy analysis is a time-consuming, labor-intensive technique that requires 70 minutes to deparaffinize and rehydrate 50 microns sections as the initial step. Manual deparaffinization was compared with two semiautomated methods using an automatic slide stainer with either a 70-minute or 35-minute schedule. Samples from 6 normal tissues and 21 tumors (13 diploid and 8 aneuploid) were prepared using all three methods and analyzed by FCM. The mean cell counts in all samples were over 10(6). The DNA indices for the three samples prepared from a given tissue showed no significant differences. Using the 70-minute automation schedule, no aneuploid peaks were lost, and the ratio of G0G1 normal cells to aneuploid tumor cells was maintained. The automation of deparaffinization can thus provide a significant reduction in the labor need to produce single-cell suspensions for FCM; it can be especially helpful when handling large numbers of tumors. At the same time, the automated procedure decreases the exposure to hazardous chemicals and lowers the chance of losing tissue.

DNA↗

PubMed1991

Paratesticular myxoma: an unusual benign intrascrotal neoplasm.

We have presented a case of paratesticular myxoma and have described the clinical history, findings on light microscopy and immunohistochemistry, and possible pathogenesis. Although primary paratesticular myxoma is a rare lesion, it should be considered in the differential diagnosis of intrascrotal mesenchymal tumors.

Adult↗

PubMed1990

The possible role of ionic species in selective biodistribution of photochemotherapeutic agents toward neoplastic tissue.

Photochemotherapeutic agents are photosensitizers that are selectively retained by neoplastic tissue. When tumor tissue containing these drugs is irradiated with visible electromagnetic radiation, the photosensitizing reaction may lead to tumor eradication, termed photodynamic therapy. Exogenous photosensitizers commonly used in clinical trials are mainly porphyrin derivatives. Phthalocyanines are currently being investigated as "second generation" photochemotherapeutic agents. The mechanism by which these photosensitizers are selectively retained in neoplastic tissue is unclear. This review examines the role of tissue and cellular pH as a factor in selective biodistribution. The pH values of normal and tumor tissue are summarized and the ionic species distribution diagram of porphyrins is presented. A two-fold mechanism of selective biodistribution is advanced, one involving normal tissue vs. tumor tissue selectivity, the other involving intracellular vs. intercellular distribution of sensitizer ionic species.

Animals↗

PubMed1990

Syndrome of a craniofacial dysostosis, limb malformation, and omphalocele.

We describe an infant with a unique combination of a severe craniofacial dysostosis and a very distinctive facies, severe limb defects, a thoracic deformity, and an omphalocele as the major anomalies. We propose that this represents a "new" syndrome of multiple congenital abnormalities.

Abnormalities, Multiple↗