Techniques for the extraction of high rectal foreign bodies by transanal minimally invasive surgery.

Removal of rectosigmoid retained foreign bodies (RFB) may require laparoscopy and often laparotomy. Proctoscopic extraction from the distal sigmoid colon and proximal rectum can be technically difficult. Using a transanal minimally invasive surgery (TAMIS) approach, RFBs can be safely removed, avoiding an abdominal operation with associated morbidity. Patients without clinical findings concerning for acute colonic perforation undergo bedside digital rectal examination and proctoscopic attempt at removal of RFB. If unsuccessful, patients undergo rectal examination under anesthesia with proctoscopy and attempted RFB removal. If the RFB cannot be easily removed, a TAMIS port is inserted into the anal canal and pneumorectum is established. A laparoscopic camera and instruments are then used to facilitate removal of the RFB. To date, TAMIS was successful in all 10 patients with RFB requiring an operation. All patients tolerated the procedure well and were discharged to home from the postoperative recovery room. Unfortunately, none of the patients presented for follow-up visits, but there were no known complications. This technique can be considered prior to laparotomy for patients with RFBs after failed digital examination with proctoscopy.

Encephalitozoon cuniculi infection in Barbary striped grass mice (Lemniscomys barbarus).

INTRODUCTION: Encephalitozoon cuniculi is an obligate intracellular microsporidian parasite that commonly induces subclinical infections in rabbits, but occurs also in a range of other species, including various rodents, carnivores, humans and birds. The present report describes encephalitozoonosis in a group of captive Barbary striped grass mice (Lemniscomys barbarus) in a zoo collection. The aetiology was confirmed by immunohistochemistry and PCR with subsequent sequencing. The source of infection is not known.

Update on regional anaesthesia in intraocular surgery.

BACKGROUND: Retrobulbar anaesthesia is a valuable alternative not only for polymorbid and haemodynamically compromised patients. Complications are rare but may be devastating. METHODS: Principally, any intraocular surgery can be made under local anaesthesia. There are only a few contraindications to regional anaesthesia such as denial against regional anaesthesia, allergy to local anaesthetics, local infection, severe orthopnea, insufficiently controlled psychiatric disorders or small children and non-cooperative patients. RESULTS: The success rate of retrobulbar anaesthesia in terms of control of intraoperative discomfort approaches 100% with an intraconal injection in 94% and a distribution of fluid into the intraconal space in 97%. CONCLUSION: Based on the recent literature, the present review compares techniques, describes possible complications and in the absence of evidence-based studies provides suggestions for the handling of patients under thrombocyte aggregation inhibitor and vitamin K antagonist therapy and anticoagulation.

Anaesthesia for castration of piglets: comparison between intranasal and intramuscular application of ketamine, climazolam and azaperone.

The aim of this study was to compare the effect of an anaesthetic combination given either intramuscularly (IM) or intranasally (IN) for castration of piglets. Forty piglets aged 4 to 7 days were randomly assigned to receive a mixture of ketamine 15 mg kg-1, climazolam 1.5 mg kg-1 and azaperone 1.0 mg kg-1, IN or IM, 10 minutes prior to castration. Physiological parameters were measured. Castration was videotaped for evaluation by 3 independent observers using a scoring system. Reaction and vocalization to the skin incision and cutting of spermatic cord was evaluated and scored (0 = no reaction, 16 = strong reaction). The IN group had a significantly higher (P < 0.01) castration score, compared to the IM group. There was an association between castration score and room temperature in the IN group (with temperatures below 18 "C associated with a higher castration scores (P < 0.001). Heart rate was significantly higher 10 minutes after castration in the IN group (P < 0.05). Respiratory rate was significantly higher in the IM group at time points -5, -1, 10, 20 and 30 (P < 0.05). The IN group was walking significantly (P < 0.0001) faster than the IM group. In conclusion, this combination provides effective anaesthesia for routine castration of newborn piglets when administered IM. IN administration provided shorter recovery times but had significantly higher castration scores.

Evaluation of the analgesic effect of lidocaine and bupivacaine used to provide a brachial plexus block for forelimb surgery in 10 dogs.

Twenty adult dogs weighing between 1.4 and 53.5 kg and aged between six months and nine years were anaesthetised and the brachial plexus was localised with the aid of a nerve stimulator. In 10 of the dogs a brachial plexus block was induced with a mixture of lidocaine and bupivacaine and the other 10 each received 0.25 ml/kg saline as a control. The end-tidal isoflurane concentration was maintained between 1.3 and 1.4 per cent during surgery for carpal arthrodesis or a fracture of the radius or ulna. Acute heart rate or blood pressure increases of 20 per cent or more were treated with 1 microg/kg fentanyl intravenously. Postoperatively, signs of pain were scored by a single blinded observer at hourly intervals until eight hours after the block had been induced, on a scale from 0 to 18. Dogs with pain scores above 5 received 0.1 to 0.2 mg/kg methadone intravenously, repeated as necessary. During surgery the control dogs received significantly more fentanyl (median 0.05 microg/kg/minute, range 0.02 to 0.20 microg/kg/minute) than the group given local anaesthetic (median 0 microg/kg/minute, range 0 to 0.02 microg/kg/minute). Postoperatively, the control group required significantly more methadone (median 0.2 mg/kg, range 0.1 to 1 mg/kg) than the treated group (median 0 mg/kg, range 0 to 0.13 mg/kg).

Dopamine D2 receptor imaging with SPECT: studies in different neuropsychiatric disorders.

The purpose of the present study is to visualize and quantify dopamine D2 receptors in the living human brain using an 123I-labeled ligand and the single photon emission computerized tomography (SPECT) technique. S-(-)-Iodobenzamide [S-(-)-IBZM] has been shown to be a highly selective ligand with high affinity for D2 receptors in experimental studies. Five millicuries (185 MBq) of 123I-labeled S-(-)-IBZM was administered intravenously to 12 control subjects, 22 parkinsonian patients under L-Dopa therapy, 12 parkinsonian patients without L-Dopa, 10 unmedicated patients with Huntington's disease, and 12 patients under different neuroleptics. Data collection with a rotating double-head scintillation camera started 1 h after injection and lasted for 50 min. In a semiquantitative approach, a ratio was calculated between mean counts per pixel in the striatum and a region in the lateral frontal cortex, which was 1.74 +/- 0.10 in the control group. A marked reduction of this ratio was found in patients with Huntington's disease (1.38 +/- 0.12; p = 0.0001), no significant changes in untreated parkinsonian patients (1.67 +/- 0.14), but a reduction in L-Dopa-treated cases (1.59 +/- 0.13; p = 0.0014). A curvilinear relationship was found between total daily dose of neuroleptics and the reduction of this ratio. Estimated receptor blockade under full neuroleptic treatment was 75-80%. S-(-)-IBZM binding was reduced with increasing age (p less than 0.01). Specific binding was reduced markedly when the racemic mixture of IBZM was used, and no specific binding was seen with the R-(+)-isomer, demonstrating the stereoselectivity of IBZM binding.(ABSTRACT TRUNCATED AT 250 WORDS)

D2 receptor blockade by flunarizine and cinnarizine explains extrapyramidal side effects. A SPECT study.

Twenty-six patients under treatment with the calcium channel blockers flunarizine (Fz) or cinnarizine (Cz) were examined-with single-photon emission computed tomography using [123I]iodobenzamide as a ligand. The striatal dopamine D2 receptor-binding potential was determined and found to be reduced by 14 to 63% (39.5 +/- 15.0%; p < 0.0001) in patients compared with age-matched control values. This reduction was larger in 12 patients with extrapyramidal symptoms and was only slowly reversible after discontinuation of treatment. Patients treated for > 6 months had significantly larger reductions than patients treated for a shorter period. Parkinsonian symptoms were only seen in patients older than 50 years. Our findings prove a neuroleptic-like action of Fz and Cz, which seems to be the major reason for their extrapyramidal side effects. Older age and long-term treatment are predisposing factors for these effects.

Myeloperoxidase-catalyzed redox-cycling of phenol promotes lipid peroxidation and thiol oxidation in HL-60 cells.

Various types of cancer occur in peroxidase-rich target tissues of animals exposed to aryl alcohols and amines. Unlike biotransformation by cytochrome P450 enzymes, peroxidases activate most substrates by one-electron oxidation via radical intermediates. This work analyzed the peroxidase-dependent formation of phenoxyl radicals in HL-60 cells and its contribution to cytotoxicity and genotoxicity. The results showed that myeloperoxidase-catalyzed redox cycling of phenol in HL-60 cells led to intracellular formation of glutathionyl radicals detected as GS-DMPO nitrone. Formation of thiyl radicals was accompanied by rapid oxidation of glutathione and protein-thiols. Analysis of protein sulfhydryls by SDS-PAGE revealed a significant oxidation of protein SH-groups in HL-60 cells incubated in the presence of phenol/H2O2 that was inhibited by cyanide and azide. Additionally, cyanide- and azide-sensitive generation of EPR-detectable ascorbate radicals was observed during incubation of HL-60 cell homogenates in the presence of ascorbate and H2O2. Oxidation of thiols required addition of H2O2 and was inhibited by pretreatment of cells with the inhibitor of heme synthesis, succinylacetone. Radical-driven oxidation of thiols was accompanied by a trend toward increased content of 8-oxo-7,8-dihydro-2'-deoxyguanosine in the DNA of HL-60 cells. Membrane phospholipids were also sensitive to radical-driven oxidation as evidenced by a sensitive fluorescence HPLC-assay based on metabolic labeling of phospholipids with oxidation-sensitive cis-parinaric acid. Phenol enhanced H2O2-dependent oxidation of all classes of phospholipids including cardiolipin, but did not oxidize parinaric acid-labeled lipids without addition of H2O2. Induction of a significant hypodiploid cell population, an indication of apoptosis, was detected after exposure to H2O2 and was slightly but consistently and significantly higher after exposure to H2O2/phenol. The clonogenicity of HL-60 cells decreased to the same extent after exposure to H2O2 or H2O2/phenol. Treatment of HL-60 cells with either H2O2 or H2O2/phenol at concentrations adequate for lipid peroxidation did not cause a detectable increase in chromosomal breaks. Detection of thiyl radicals as well as rapid oxidation of thiols and phospholipids in viable HL-60 cells provide strong evidence for redox cycling of phenol in this bone marrow-derived cell line.

Heterosupramolecular chemistry: programmed pseudorotaxane assembly at the surface of a nanocrystal.

Gold nanocrystals, stabilized by thiols covalently bound to a dibenzo[24]crown-8 moiety, have been programmed to recognize and selectively bind dibenzylammonium cations in solution. This results in a self-organization process at the surface of a nanocrystal with the assembly of a pseudorotaxane (see picture).

Potent somatostatin undecapeptide agonists selective for somatostatin receptor 1 (sst1).

A family of analogues of des-AA(1,2,5)-[DTrp(8)/D2Nal(8)]-SRIF that contain a 4-(N-isopropyl)-aminomethylphenylalanine (IAmp) at position 9 was identified that has high affinity and selectivity for human somatostatin receptor subtype 1 (sst1). The binding affinities of des-AA(1,2,5)-[DTrp(8),IAmp(9)]-SRIF (c[H-Cys-Lys-Phe-Phe-DTrp-IAmp-Thr-Phe-Thr-Ser-Cys-OH], CH-275) (7), des-AA(1,5)-[Tyr(2),DTrp(8),IAmp(9)]-SRIF (CH-288) (16), des-AA(1,2,5)-[Tyr(7),DTrp(8),IAmp(9)]-SRIF (23), and des-AA(1,2,5)-[DTrp(8),IAmp(9),Tyr(11)]-SRIF (25) are about (1)/(7), (1)/(4), (1)/(125), and (1)/(4) that of SRIF-28 (1) to sst1, respectively, about (1)/(65), (1)/(130), <(1)/(1000), and <(1)/(150) that of 1 to sst3, respectively, and about or less than (1)/(1000) that of 1 to the other three human SRIF receptor subtypes. A substitution of DTrp(8) by D2Nal(8) in 7 to yield des-AA(1,2,5)-[D2Nal(8),IAmp(9)]-SRIF (13) and in 16 to yield des-AA(1,5)-[Tyr(2),D2Nal(8),IAmp(9)]-SRIF (17) was intended to increase chemical stability, selectivity, and affinity and resulted in two analogues that were less potent or equipotent with similar selectivity, respectively. Carbamoylation of the N-terminus as in des-AA(1,2,5)-[DTrp(8),IAmp(9),Tyr(11)]-Cbm-SRIF (27) increased affinity slightly as well as improved selectivity. Monoiodination of 25 to yield 26 and of 27 to yield 28 resulted in an additional 4-fold increase in affinity at sst1. Desamination of the N-terminus of 17 to yield 18, on the other hand, resulted in significant loss of affinity. Attempts at reducing the size of the ring with maintenance of selectivity failed in that des-AA(1,4,5,13)-[Tyr(2),DTrp(8),IAmp(9)]-SRIF (33) and des-AA(1,4,5,6,12,13)-[Tyr(2),DTrp(8),IAmp(9)]-SRIF (34) progressively lost affinity for all receptors. Both des-AA(1,2,5)-[DTrp(8),IAmp(9),Tyr(11)]-Cbm-SRIF (27) and des-AA(1,2,5)-[DCys(3),DTrp(8),IAmp(9),Tyr(11)]-Cbm-SRIF (29) show agonistic activity in a cAMP assay; therefore, the structural basis for the agonist property of this family of analogues is not contingent upon the chirality of the Cys residue at position 3 as shown to be the case in 18-membered ring SRIF octapeptides. None of the high affinity structures described here showed receptor antagonism. We have prepared the radiolabeled des-AA(1,2,5)-[DTrp(8),IAmp(9),(125)ITyr(11)]-SRIF ((125)I-25) and des-AA(1,2,5)-[DTrp(8),IAmp(9), (125)ITyr(11)]-Cbm-SRIF ((125)I-27), used them as in vitro tracers, and found them to be superior to des-AA(1,5)-[(125)ITyr(2),DTrp(8),IAmp(9)]-SRIF ((125)I-16) for the detection of sst1 tumors in receptor autoradiography studies.

Iodine-123-epidepride-SPECT: studies in Parkinson's disease, multiple system atrophy and Huntington's disease.

UNLABELLED: Epidepride is a benzamide derivative with very high affinity for D2 receptors, which, in its [123I]-labeled form, can be used for SPECT. The aim of this study was to evaluate the usefulness and accuracy of [123I]epidepride-SPECT for the differential diagnosis of movement disorders. METHODS: SPECT imaging with a triple-headed scintillation camera was performed in 9 patients with Parkinson's disease, 9 patients with probable multiple system atrophy (MSA), 1 patient with progressive supranuclear palsy, 16 patients with Huntington's disease (HD) and 14 controls, 3 hr after the intravenous injection of 3.7 +/- 1.3 mCi of [123I]epidepride. The striatum-to-cerebellum ratio - 1, reflecting the specific-to-nondisplaceable binding ratio, was used as a semiquantitative measure of D2 receptor binding. RESULTS: Kinetic studies showed peak striatal uptake about 3 hr postinjection and a slow decline thereafter. The striatum-to-cerebellum ratio - 1 was significantly reduced in MSA (11.8 +/- 3.9, compared to controls, 19.0 +/- 6.3; p < 0.01) and in patients with HD (8.8 +/- 3.2; p < 0.00005) but normal in Parkinson's disease (15.8 +/- 3.6; not significant). A high interindividual variation of specific striatal epidepride binding (striatum - cerebellum; cpm/mCi x kg) was found in controls and in all patient groups. The interindividual variation of striatum-to-cerebellum ratios was lower but still considerable. In half of the MSA patients, the specific-to-nondisplaceable binding ratio fell within the range of controls. The use of various cortical reference regions did not improve discrimination between MSA and controls or Parkinson's disease patients, respectively. The discrimination of HD patients from controls was better, with overlap in only two cases. In one HD patient, calculation of the striatum-to-cerebellum ratio was almost impossible due to extremely low nonspecific binding. Possible explanations for the large variation of the ratios, resulting in an overlap between controls and different patient groups, are very low counting rates in the reference region and the fact that a transient binding equilibrium may not be achieved after bolus injection of epidepride. CONCLUSION: Epidepride appears to be a useful SPECT ligand for studying dopamine D2 receptors. However, its markedly higher specific-to-nondisplaceable binding ratio in comparison to those of iodobenzamide or other D2 ligands did not result in a better discrimination between different basal ganglia disorders. The calculation of plasma input curves and volumes of distribution might improve the accuracy of [123I]epidepride-SPECT.

Imaging of dopamine transporters with iodine-123-beta-CIT and SPECT in Parkinson's disease.

UNLABELLED: The aim of the present study was to demonstrate the degeneration of the dopaminergic nigrostriatal pathway in Parkinson's disease by using the cocaine derivative [123I]beta-CIT (2-beta-carbomethoxy-3-beta(4-iodophenyl)-tropane or RTI-55) and SPECT and to relate the findings to the severity of the disease (Hoehn and Yahr scale, H/Y) and to clinical data such as motor score and activities of daily living. METHODS: Thirteen volunteers and 47 patients with idiopathic Parkinson's disease (PD) of H/Y Stage I-V (I:n = 16, II:n = 6, III:n = 14, IV:n = 9, V:n = 2) were investigated. Acquisitions were performed 2, 4, 16, 20 and 24 hr postinjection. ROIs were drawn over the striatum and the cerebellum. Specific beta-CIT binding was defined as striatal minus cerebellar binding. The ratio of specific over nondisplaceable binding (striatum/cerebellum-1) was determined as well as the percent deviation of this ratio from age-expected control values. RESULTS: The time-activity curve of striatal [123I]beta-CIT binding demonstrated a maximum around 20 hr postinjection in controls and a peak 4 hr postinjection in PD patients. Ratios differed significantly between the two groups. A significant correlation existed between this ratio and clinical measures. Hemiparkinsonian patients revealed significantly diminished [123I]beta-CIT binding not only contralateral to the clinically affected but also contralateral to the clinically unaffected side. [123I]beta-CIT binding showed a significant decrease in comparison to age-expected values ranging from 36% in H/Y stage 1 to 71% in H/Y stage V. CONCLUSION: The present study demonstrates that it is possible to visualize and quantify the degeneration of dopaminergic nigrostriatal neurons in PD using [123I]beta-CIT and SPECT with good correlation to clinical parameters.

Bone marrow stromal cells regulate caspase 3 activity in leukemic cells during chemotherapy.

The interaction between leukemic cells and stromal cells of the bone marrow microenvironment has been shown to enhance leukemic cell survival during exposure to chemotherapeutic agents. In the current study we investigated whether association of B lineage acute lymphoblastic leukemic cells with human bone marrow stromal cells altered caspase activation during chemotherapy treatment. Following treatment with Ara-C or VP-16 in vitro, caspase 3 activity in leukemic cells was consistently reduced by co-culture of leukemic cells with human bone marrow stromal cell layers. These observations suggest that the protective effect of the bone marrow microenvironment on leukemic cells may be due, in part, to regulation of caspase 3 activity.

Failure of PHA-stimulated i(12p) lymphocytes to divide in Pallister-Killian syndrome.

The diagnosis of Pallister-Killian syndrome (PKS) is confirmed by tissue-specific mosaicism of i(12p). The isochromosome is found in skin fibroblasts and bone marrow, but rarely in peripheral lymphocytes. The nature of the isochromosome loss was evaluated using 2 techniques: micronucleus formation for anaphase lag and in situ DNA hybridization for mosaicism in interphase cells. Cells from serial cultured fibroblasts, peripheral blood lymphocytes, and bone marrow from 4 PKS patients were used for the above analysis. Micronucleus formation was similar for PKS and normal diploid cultures, ruling out loss of i(12p) by anaphase lag as the major mechanism of in vitro mosaicism. In situ hybridization using an alpha satellite DNA probe for chromosome 12 was used to examine the presence of the i(12p) in interphase fibroblasts from 1 patient and lymphocytes from 2 patients (age 8 weeks and 1 day). The i(12p) was present in a significantly higher proportion of interphase nuclei in peripheral lymphocytes than in metaphase, suggesting the initial loss of the isochromosome is exaggerated in metaphase by selective division in vitro. In situ hybridization of peripheral lymphocyte interphase cells with chromosome 12 specific probes may be a useful supplemental procedure for the diagnosis of PKS, at least in the newborn infant.

Meiotic consequences of pericentric inversions of chromosome 13.

A case is presented demonstrating meiotic consequences of inheritance of a pericentric inversion, inv(13)(p13q21), and suggesting, together with other similar reports reviewed, that certain manifestations (highly arched palate, long philtrum, polydactyly, microphthalmia, and capillary hemangiomata) result from duplication of the distal 13q while others (cleft lip/palate, scalp defects, congenital heart disease) result from duplication of the proximal 13q.

Detection of pericentric inversion of X chromosome in a male fetus.

Amniocentesis on a 32-year-old woman at risk for trisomy 21 by maternal serum triple screen showed a 46,Y,inv(X) (p22.1q24) karyotype in all cells analyzed. A blood sample was obtained from the mother for cytogenetic evaluation. Since she had the same inversion, DNA replication studies were performed to determine if the X inactivation pattern was random or not, since skewed inactivation of the inverted X might suggest that the breakpoints disrupted functional genes. DNA replication studies demonstrated that 68% of mother's cells with the inverted X were active, suggesting random X inactivation. The random X inactivation pattern suggested that the inversion is probably balanced and should not affect the fetus. A normal male was delivered at 40 weeks gestation.

Increased sister chromatid exchange frequency at Xq27 site in affected fragile X males.

Sister chromatid exchange (SCE) was evaluated in peripheral blood lymphocytes cultured from normal subjects, fragile X carrier females, and fragile X affected males and in general did not differ among all subjects whether cells were grown in thymidine-deficient or complete medium. However, at the Xq27 site, SCE was significantly increased for fragile X affected males, particularly in cells grown in thymidine-deficient medium.

Down syndrome consequent to a cryptic maternal 12p;21q chromosome translocation.

A 9-year-old, mildly mentally retarded girl presented with phenotypic manifestations of Down syndrome. G-banded chromosomal analyses of peripheral blood lymphocytes from the patient and her parents, and skin fibroblasts from the patient, did not detect any abnormality. Molecular analysis of 15 highly polymorphic chromosome 21 dinucleotide repeat markers demonstrated a partial duplication of the Down syndrome critical region (D21S55, subband 21q22.2) of maternal origin in the patient. The segmental trisomy was confirmed by FISH analysis using the cosmid probe D21S55. Further analysis demonstrated that the trisomy was due to segregation of an apparently balanced cryptic translocation from the mother. The patient's karyotype is 46,XX,-12,tder(12)t(12;21)(p13.1;q22.2)mat.

Inability to induce fragile sites at CTG repeats in congenital myotonic dystrophy.

Myotonic dystrophy (DM) is a trinucleotide repeat syndrome which can contain 50 to over 2,000 CTG repeats in affected individuals, but does not express a fragile site. Although one prior study [Jalal et al., Am J Med Genet 46:441-443, 1993] did not find evidence of fragility at 19q13.3 in six individuals affected with DM using induction protocols for folate sensitive fragile sites, other chemicals may induce fragile site expression at this site. In an attempt to induce fragile sites at 19q13.3, blood cultures from four congenital DM cases and four control individuals treated with fluorodeoxyuridine (folate-sensitive rare fragile sites), bromodeoxyurdine (rare and common fragile sites), aphidicolin (common fragile sites), and 5-azacytidine (common fragile sites) were harvested using routine cytogenetic technique. Slides were solid stained and 100 cells were examined for fragile site expression, particularly on F group chromosomes. The latter were photographed prior to destaining and G-banded to verify chromosome and band location of breakage. No culture conditions induced a fragile site at band 19q13.3 at > 1% expression in patients with congenital DM. Our results suggest that CTG repeats, even when present in > 1,000 copies, may behave differently from other large expansions which are associated with fragile sites. The CTG repeats in DM are not associated with a methylated CpG island, as are folate-sensitive fragile sites, which most likely plays a role in the expression of fragile sites at the trinucleotide repetitive site.

Mosaicism in Pallister i(12p) syndrome.

The clinical diagnosis of Pallister syndrome in a 1-day-old white boy was confirmed by the presence of i(12p) in 100% of cells on direct bone marrow analysis. This is the second Pallister syndrome case in which cytogenetic diagnosis was made in bone marrow cells during the neonatal period. Other tissues analyzed in our patient included peripheral blood PHA-stimulated cultured lymphocytes and postmortem skin and lung cultured fibroblasts with 3%, 98.5%, and 97.5% of cells containing the i(12p), respectively. Serial skin fibroblast cultures re-established from frozen cells were analyzed sequentially over time for the isochromosome. There was slight reduction in the proportion of i(12p) cells until passage 15 with plateauing of the proportion of i(12p) cells at about 80% until culture senescence. Our review of such cytogenetic analyses suggests that in vivo and perhaps also in vitro isochromosome loss best explains the intra- and inter-tissue specific chromosomal mosaicism in the i(12p) syndrome. In any event, our results indicate that confirmation of the diagnosis in the neonatal period is possible by direct cytogenetic analysis of bone marrow.