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Biomedical subjects

J Dent

Publications and source records attributed to J Dent.

At least 271 records · Page 15Linked to original sources
PubMed1985

Tone of canine ileocolonic junction: topography and response to phasic contractions.

We wished to define the physiology of the canine ileocolonic sphincter (ICS) and to examine function in relation to the region's anatomy. Prolonged recordings of tone at the ICS were made from seven dogs with isolated ileocolonic loops, and the effects of ileal and colonic distension on sphincteric tone were assessed. In acute experiments, pull-through pressures were measured at the ICS, and the location of the high-pressure zone was related to the region's anatomy. Basal tone at the ICS of approximately 30 cmH2O was confirmed; tone was augmented by colonic and ileal distension. The high-pressure zone was always centered on the anatomic ICS, but it extended into the adjacent ileum and colon for a total length of 2.0 cm (range 1.5-3.0 cm). Phasic contractions contributed to the maintenance of tone at the ICS, and a coordinated pattern of phasic contractions appears to contribute to the sphincteric properties of the region.

Animals↗
PubMed1985

High-resolution analysis of von Willebrand factor multimeric composition defines a new variant of type I von Willebrand disease with aberrant structure but presence of all size multimers (type IC).

In Type I von Willebrand disease, the whole series of von Willebrand factor (vWF) multimers is present in plasma, but all are decreased in quantity. No structural abnormality of individual multimers has been demonstrated so far in these patients. We now describe five individuals, from two unrelated families, who had this form of the disease and in whom the complex banding pattern of each vWF multimer was markedly abnormal. Inheritance was autosomal dominant and the clinical expression was mild. A bleeding history was elicited in three of the patients and included recurrent epistaxis, menometrorrhagia, and bleeding following tooth extraction. Replacement therapy had never been required. Although vWF levels in plasma were within the normal range in all of them, the ristocetin cofactor activity was decreased in four, and the bleeding time was prolonged in three. Analysis of vWF multimeric structure by agarose gel electrophoresis, including a newly developed high-resolution technique, demonstrated that the main band of each multimer was present, but a second, well-defined band always seen in normal individuals was missing in the patients. Two additional bands had altered mobility and were less well defined than in normal subjects, and a fifth, less intense band was also undetectable in the patients. Treatment with 1-deamino-8-D-arginine vasopressin (DDAVP) was assessed in two patients. It caused the circulating levels of vWF to increase and correct the bleeding time, but did not alter the structural abnormality. This study describes, therefore, a new variant form of Type I von Willebrand disease with aberrant structure of individual repeating multimers and an associated functional abnormality of vWF. In keeping with previously accepted terminology, the designation of Type IC von Willebrand disease has been adopted for this new variant.

Adult↗
PubMed1985

Type IIB Tampa: a variant of von Willebrand disease with chronic thrombocytopenia, circulating platelet aggregates, and spontaneous platelet aggregation.

Type IIB von Willebrand disease is characterized by enhanced ristocetin-induced platelet aggregation and absence of large von Willebrand factor multimers from plasma. An alteration of the von Willebrand factor molecule resulting in increased reactivity with platelets appears to be the basis for these abnormalities. We have now identified a new variant of type IIB von Willebrand disease in a family in which the four affected members also have chronic thrombocytopenia, in vivo platelet aggregate formation, and spontaneous platelet aggregation in vitro. In spite of repeatedly prolonged bleeding times and persistent thrombocytopenia, their bleeding diathesis is only moderate.

Adult↗
PubMed1984

Pregnancy after cytotoxic chemotherapy for gestational trophoblastic tumours.

To examine the possibility that cytotoxic drugs may cause sterility or congenital malformations in the offspring of women of childbearing age who are cured of cancer a study was conducted of the obstetric histories of 445 long term survivors treated in this unit with chemotherapy for gestational trophoblastic tumours between 1958 and 1978. After completing treatment 97% of those who wished for a pregnancy (49% of all women studied) conceived and 86% had at least one live birth. All these women had received methotrexate. Of the 47 women who wished to conceive and whose combination therapy included cyclophosphamide, 37 (79%) had a live birth. Women who received three or more drugs were less likely to have a live birth than those who received methotrexate alone or with only one other drug (p less than 0.001). There was no statistically significant excess of congenital malformations. These results are strong evidence that the cytotoxic drug regimens used in this unit for treating gestational trophoblastic tumours are compatible with the preservation of fertility in most women and not associated with any increase in congenital abnormalities.

Abnormalities, Drug-Induced↗
PubMed1984

The pharmacokinetics of orally absorbed cefuroxime compared with amoxycillin/clavulanic acid.

The pharmacokinetics of a new orally absorbed pro-drug of cefuroxime were compared with those of co-administered amoxycillin and clavulanic acid in six healthy male volunteers. Doses of 600 mg of acetoxyethyl cefuroxime and 500 mg amoxycillin plus 250 mg clavulanic acid were each administered for ten doses 8 hourly. Tissue penetration after the first dose of the antibiotic was estimated by a cantharides blister method. The faecal flora of the volunteers was studied throughout the study. The pharmacokinetics of cefuroxime and amoxycillin were very similar, peak levels of about 6.4 mg/l being found between 2 and 2.5 h after administration. The peak serum level of clavulanic acid was 4.3 mg/l at 1.25 h after administration. The serum half-lives were about 1.1 h for all three agents. No drug accumulation occurred over the four days of the study. The 0-8 h urinary recovery of cefuroxime was 30%. All three agents penetrated the blister fluid rapidly, the main peak levels being 64% of the peak serum level for cefuroxime, 72% for amoxycillin and 55% for clavulanic acid. The incidence of side effects was similar for each regimen. Three volunteers having diarrhoea after cefuroxime showed significant alterations in their bowel flora.

Adult↗
PubMed1984

The pharmacokinetics and tissue penetration of ofloxacin.

The pharmacokinetics of the 4-quinolone agent, ofloxacin, were studied in six healthy volunteers, following a 600 mg oral dose. The levels of the compound were measured by a microbiological assay in serum, blister fluid and urine. The compound was rapidly absorbed, the mean maximum concentration of ofloxacin being 10.7 mg/l at 1.2 h. The mean serum elimination half-life was 7 h and 80.3% of the administered compound was recovered in the urine by 48 h. Ofloxacin penetrated the blister fluid well, the mean peak level being 5.2 mg/l at 5.3 h.

Adult↗
PubMed1984

Pharmacokinetics and tissue penetration of enoxacin.

The pharmacokinetics of the quinolone enoxacin were studied after a 600-mg oral dose was given to each of six male volunteers. The levels of the compound were measured in serum, blister fluid, and urine. Absorption was variable, with peak levels (mean, 3.7 micrograms/ml) being attained between 0.75 and 3.0 h (mean, 1.9 h). The serum elimination half-life was 6.2 h, and 71.6% of the drug was recovered in the urine by 48 h. Enoxacin penetrated blister fluid well, the mean percent penetration being 78.4%.

Adult↗
PubMed1984

Pharmacokinetics of intravenously administered ciprofloxacin.

A 100-mg dose of ciprofloxacin was given as an intravenous bolus injection to each of six healthy volunteers, after which the levels of this agent were measured in serum, blister fluid, and urine. After administration, distribution of ciprofloxacin was very rapid, and the mean distribution volume was very large (177 liters). The mean terminal serum half-life was 4.0 h. The agent penetrated blister fluid rapidly, with the mean maximum level being 0.53 micrograms/ml at 30 min, after which time the blister levels exceeded those in serum. The 48-h urinary recovery of ciprofloxacin was about 80%.

Adult↗
PubMed1984

Acquired von Willebrand's disease in the myeloproliferative syndrome.

An acquired hemorrhagic disorder developed in two patients in association with postsplenectomy thrombocytosis and leukocytosis during the course of the myeloproliferative syndrome. The presence of acquired von Willebrand's disease in these individuals was demonstrated by a decrease or absence of the larger von Willebrand factor (vWF) multimers, alteration of the repeating vWF multimeric "triplet," decreased ristocetin cofactor activity (vWF:RCo), and prolonged bleeding time. The bleeding stopped in both patients after treatment with either 1-deamino-[8-D-arginine]-vasopressin (DDAVP) or Cohn fraction I. Treatment with thrombocytapheresis and azathioprine or busulfan resulted in reduction of the elevated platelet and white cell counts and was associated with partial correction of the vWF abnormalities and remission of the hemostatic abnormalities. In five additional patients with the myeloproliferative syndrome, but without bleeding symptoms, large multimers of plasma vWF were diminished also. These findings suggest that acquired von Willebrand's disease should be considered when a bleeding diathesis develops during the course of the myeloproliferative syndrome.

Adult↗
PubMed1984

Distinctive patterns of interdigestive motility at the canine ileocolonic junction.

Studies of interdigestive motor activity in the distal ileum, ileocolonic sphincter, and proximal colon were performed in two groups of dogs: (i) in those with ileocolonic loops that maintained neuromuscular continuity with the proximal intestine, we used an intraluminal side-hole assembly; (ii) in those with intact bowel, we attached extraluminal strain gauge transducers. Both groups of animals were equipped also with serosal electrodes. Positioning of motor sensors could be defined accurately by (a) a clear separation of rhythmic frequencies between those of the distal ileum (mean 10.8 cycles/min) and proximal colon (mean 6.2 cycles/min) and (b) the characteristic motor patterns of the ileocolonic sphincter. Analysis of motor activity in the segment demonstrated four distinct patterns: (i) irregular, apparently random phasic waves, (ii) rhythmic bursts of contractions corresponding to phase III of the migrating motor complex, (iii) other slowly propagated bursts of rhythmic activity (mean duration 3.6 min) recurring on average every 10 min, and (iv) single, prolonged (mean duration 16.7 s), high amplitude (mean 271 cmH2O) waves that propagated rapidly ("prolonged propagated contractions"). The latter two patterns appear unique to, or unusually prominent in, this region. A high degree of motor coordination between the distal ileum, ileocolonic sphincter, and proximal colon was also recognized. Thus, the patterns of motor activity suggest a specialized function for the distal 30 cm of ileum, the ileocolonic sphincter, and the proximal colon. These unique and coordinated patterns of motility deserve further exploration, especially in relation to ileocolonic transit and actions of the sphincter as a barrier to colo-ileal reflux.

Action Potentials↗
PubMed1983

No increase in second tumors after cytotoxic chemotherapy for gestational trophoblastic tumors.

We investigated the incidence of second tumors after cytotoxic chemotherapy in 457 long-term survivors treated for choriocarcinoma or an invasive mole between 1958 and 1978. Treatment was given according to regular intermittent schedules and over a mean period of four months, with no maintenance. Methotrexate was given to all but two patients, and 261 (57 per cent) also received other cytotoxic drugs, most commonly dactinomycin, vincristine, cyclophosphamide, mercaptopurine, and 6-azauridine. After a mean period of 7.8 years since the beginning of treatment and a total of 3522 patient-years of risk, second neoplasms had developed in only two women (acute leukemia in one and carcinoma of the breast in the other). This figure is less than the number of cases of cancer that would have been expected (3.5) in this group and suggests that the use of methotrexate as chemotherapy for choriocarcinoma is not carcinogenic in the medium term.

Adult↗
PubMed1983

Problems of interpretation of serum concentrations of alpha-foetoprotein (AFP) in patients receiving cytotoxic chemotherapy for malignant germ cell tumours.

Serial determinations of serum alpha-foetoprotein (AFP) concentrations are well established in monitoring the response to therapy of malignant germ cell tumours. Using a radioimmunoassay (RIA) with a sensitivity down to 2kul-1 the majority (57%) of 28 patients with non-AFP producing germ cell tumours had measurable immunologically-reactive AFP in their serum while on treatment. Follow-up for 11-43 months (mean 27) without evidence of tumour activity indicated that this immunologically-reactive AFP was unlikely to be produced by tumour. In patients where the initial serum AFP was raised prior to chemotherapy the AFP concentration did not fall to the normal range at the end of the treatment in 16 (32%) of 41 patients. Follow-up of these patients for 9-48 months (mean 27) has resulted in 5 (12%) relapses in this group. Serum AFP greater than 20kul-1 three months after stopping chemotherapy was a good indicator of residual active tumour and 4 (57%) of 7 patients in this group relapsed. The production of detectable serum AFP is probably related to the type of chemotherapy used and only 7 (14%) of 51 patients treated for gestational choriocarcinoma had detectable AFP concentrations while on cytotoxic chemotherapy. The problem of interpretation of serum AFP concentration in patients with malignant germ cell tumour stresses the need to determine whether there are differences between AFP produced by germ cell tumours and that produced at other sites as a basis for a sensitive assay system able to discriminate between them.

Adolescent↗
PubMed1983

Pharmacokinetics and tissue penetration of ticarcillin combined with clavulanic acid.

A combination of 3 g of ticarcillin and 200 mg of clavulanic acid was administered intravenously to six healthy male volunteers, after which the concentrations of these agents in serum and blister fluid were measured. The ratio of the two drugs in serum varied from 15:1 (ticarcillin-clavulanic acid) at the time of administration to 28:1 at 30 min and 62:1 at 5 h after injection. Both agents penetrated blister fluid rapidly, the ratio being 33:1 at 1 h and 66:1 at 3 h. The elimination rates of these agents were different, but for each compound they were similar in serum and blister fluid.

Adult↗
PubMed1983

Intraperitoneal penetration of cefotetan.

The intraperitoneal penetration of cefotetan was studied after a 1-g intravenous injection in 25 patients undergoing elective gastrointestinal surgery. Levels of peritoneal fluid were high within 10 min after administration and increased to 44% of the serum levels after 30 min, rising to 115% at 3 h. The mean concentration of cefotetan between 3 and 5 h after administration was 32.3 micrograms/ml. These findings suggest that 1 g of cefotetan administered before abdominal surgery would result in intraperitoneal cefotetan levels necessary to inhibit susceptible pathogens for 5 h or more.

Adult↗
PubMed1983

Pharmacokinetics and tissue penetration of ciprofloxacin.

A 500-mg dose of the quinoline ciprofloxacin was administered orally to each of six healthy male volunteers, after which the concentrations of this agent in serum and blister fluid were measured. Absorption appeared to be rapid, with a mean peak level of 2.4 micrograms/ml attained 1.25 h after administration. The serum elimination half-life was 3.9 h. The agent penetrated blister fluid well, the percent penetration being 57%. Urinary recovery of ciprofloxacin was 30%.

Adult↗
PubMed1983

Myoelectric activity and intraluminal pressure of the canine ileocolonic sphincter.

We constructed ileocolonic loops of distal ileum, ileocolonic sphincter, and proximal colon in 5 dogs; neuromuscular continuity was maintained between loop and intact bowel by a bridge of tunica muscularis. To study ileocolonic sphincter function, we recorded myoelectric activity from subserosal electrodes and intraluminal pressures from perfused catheters and a sleeve sensor. Recordings included at least one interdigestive myoelectric complex and four postprandial hours. Ileal slow waves were recorded from the loop and the ileocolonic sphincter; most interdigestive myoelectric complexes were propagated to the ileocolonic sphincter. Intraluminal pressures at the ileocolonic sphincter fluctuated phasically (mean 12.5 cycles/min) for 72% of recording time during fasting and 81% postprandially. Tonic pressures at the ileocolonic sphincter were higher during fasting (31 +/- 18 cmH2O; p less than 0.05) than postprandially (24 +/- 20 cmH2O); moreover, tonic pressures fluctuated more during fasting than after food. Tonic elevations of pressure were prolonged (mean duration 28.5 min) concomitant with arrival of phase 3 of interdigestive myoelectric complexes at the ileocolonic sphincter. Thus the ileocolonic sphincter participates in both the myoelectric and motor components of the interdigestive cycle and exhibits an intense phasic and tonic response to phase 3. The association of tonic pressure and intense phasic contractions may serve to retard and segment ileal chyme. On the other hand, the presence of rapidly propagated phasic pressures in the region may provide the basis for propulsive function. In this way, these unique motor events will facilitate two distinct functions of the region, namely the alternate retarding and forward propulsion of chyme.

Animals↗